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Sample records for 55-200 cgg repeats

  1. Lambda Exonuclease Digestion of CGG Trinucleotide Repeats

    PubMed Central

    Conroy, R.S.; Koretsky, A.P.; Moreland, J.

    2011-01-01

    Fragile X syndrome and other triplet repeat diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. Using magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and narrower distribution of rates and a higher frequency of pausing was observed. PMID:19562332

  2. Sequestration of DROSHA and DGCR8 by expanded CGG RNA repeats alters microRNA processing in fragile X-associated tremor/ataxia syndrome.

    PubMed

    Sellier, Chantal; Freyermuth, Fernande; Tabet, Ricardos; Tran, Tuan; He, Fang; Ruffenach, Frank; Alunni, Violaine; Moine, Herve; Thibault, Christelle; Page, Adeline; Tassone, Flora; Willemsen, Rob; Disney, Matthew D; Hagerman, Paul J; Todd, Peter K; Charlet-Berguerand, Nicolas

    2013-03-28

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder caused by the expansion of 55-200 CGG repeats in the 5' UTR of FMR1. These expanded CGG repeats are transcribed and accumulate in nuclear RNA aggregates that sequester one or more RNA-binding proteins, thus impairing their functions. Here, we have identified that the double-stranded RNA-binding protein DGCR8 binds to expanded CGG repeats, resulting in the partial sequestration of DGCR8 and its partner, DROSHA, within CGG RNA aggregates. Consequently, the processing of microRNAs (miRNAs) is reduced, resulting in decreased levels of mature miRNAs in neuronal cells expressing expanded CGG repeats and in brain tissue from patients with FXTAS. Finally, overexpression of DGCR8 rescues the neuronal cell death induced by expression of expanded CGG repeats. These results support a model in which a human neurodegenerative disease originates from the alteration, in trans, of the miRNA-processing machinery.

  3. AGG interspersions within the FMR1 CGG repeat: Mechanisms and models of triplet repeat instability

    SciTech Connect

    Eichler, E.E.; Nelson, D.L.

    1994-09-01

    Fragile X syndrome CGG repeat alleles are typically classified as normal, premutation, or full mutation based on the length of the repeat in the 5{prime} UTR of the FMR1 gene. The distinction between high-end normals and low-end premutation alleles, however, is not always clear since repeats of similar size differ markedly in their intergenerational stability. This fact suggest that differences in sequence content may play a key role in determining an allele`s predisposition to instability. It has been postulated that the loss of AGG interruptions within the CGG tract may trigger this instability. To test this model, we have developed a simple indirect method to determine the presence or absence of internal AGGs within the FMR1 CGG repeat tract. Analysis of 84 human X chromosomes for the presence of interrupting AGG trinucleotides revealed that most alleles possess two interspersed AGGs at a periodicity of 9 or 10 CGGs. The longest tract of uninterrupted CGG repeats is usually found at the 3{prime} end indicating that variation in the length of the repeat is polar. Alleles containing between 34 and 55 repeats, with documented unstable transmissions, were shown to have lost one or both AGG interruptions when compared to stable alleles of similar length. These comparisons define an instability threshold between 34 and 38 uninterrupted CGG repeats. Analysis of premutation alleles in fragile X syndrome carriers reveals that 70% of these alleles contain a single AGG interruption. Population studies confirm that such highly punctuated FMR1 CGG repeats are virtually static in terms of length variation. These data suggest that the loss of an AGG is an important mutational event in the generation of unstable alleles predisposed to the fragile X syndrome. Loss of AGG trinucleotides and polarized variability support Okazaki fragment slippage as a model for CGG repeat instability and hyperexpansion.

  4. MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats

    PubMed Central

    Tan, Huiping; Poidevin, Mickael; Li, He; Chen, Dahua; Jin, Peng

    2012-01-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder, has been recognized in older male fragile X premutation carriers and is uncoupled from fragile X syndrome. Using a Drosophila model of FXTAS, we previously showed that transcribed premutation repeats alone are sufficient to cause neurodegeneration. MiRNAs are sequence-specific regulators of post-transcriptional gene expression. To determine the role of miRNAs in rCGG repeat-mediated neurodegeneration, we profiled miRNA expression and identified selective miRNAs, including miR-277, that are altered specifically in Drosophila brains expressing rCGG repeats. We tested their genetic interactions with rCGG repeats and found that miR-277 can modulate rCGG repeat-mediated neurodegeneration. Furthermore, we identified Drep-2 and Vimar as functional targets of miR-277 that could modulate rCGG repeat-mediated neurodegeneration. Finally, we found that hnRNP A2/B1, an rCGG repeat-binding protein, can directly regulate the expression of miR-277. These results suggest that sequestration of specific rCGG repeat-binding proteins could lead to aberrant expression of selective miRNAs, which may modulate the pathogenesis of FXTAS by post-transcriptionally regulating the expression of specific mRNAs involved in FXTAS. PMID:22570635

  5. Genetic variation and evolutionary stability of the FMR1 CGG repeat in six closed human populations

    SciTech Connect

    Eichler, E.E.; Nelson, D.L.

    1996-07-12

    In an attempt to understand the allelic diversity and mutability of the human FMR1 CGG repeat, we have analyzed the AGG substructure of this locus within six genetically-closed populations (Mbuti pygmy, Baka pygmy, R. surui, Karitiana, Mayan, and Hutterite). Most alleles (61/92 or 66%) possessed two AGG interspersions occurring with a periodicity of one AGG every nine or ten CGG repeats, indicating that this pattern is highly conserved in all human populations. Significant differences in allele distribution were observed among the populations for rare variants possessing fewer or more AGG interruptions than the canonical FMR1 CGG repeat sequence. Comparisons of expected heterozygosity of the FMR1 CGG repeat locus with 30 other microsatellite loci, demonstrated remarkably similar levels of polymorphism within each population, suggesting that most FMR1 CGG repeat alleles mutate at rates indistinguishable from other microsatellite loci. A single allele (1 out of 92) was identified with a large uninterrupted tract of pure repeats (42 pure CGG triplets). Retrospective pedigree analysis indicated that this allele had been transmitted unstably. Although such alleles mutate rapidly and likely represent evolving premutations, our analysis suggests that in spite of the estimated frequency of their occurrence, these unstable alleles do not significantly alter the expected heterozygosity of the FMR1 CGG repeat in the human population. 45 refs., 1 fig., 2 tabs.

  6. Deletions in the CGG repeat region of the FMR1 gene

    SciTech Connect

    Graaff, E. de; Oostra, B.A.; Meijer, H.

    1994-09-01

    The fragile X syndrome is the most frequent cause of inherited mental retardation. A remarkable feature of FMR1, the gene involved in the fragile X syndrome, is the presence of a polymorphic (CGG){sub n} repeat in the first exon of the gene. In patients this repeat is expanded to over 200 repeats. The expansion results in methylation of the CpG island 250 bp upstream of this repeat, leading to the absence of FMR1 mRNA and protein, thus resulting in the fragile X phenotype. We have found that the instability of the repeat is not restricted to the CGG repeat itself but expands to the flanking region as well. Firstly, we have identified a family in which 4 males with the fragile X clinical phenotype had a deletion immediately 5{prime} of the CGG repeat. Sequencing the deletion junction revealed that the AGG triplets that normally intersperse the CGG repeat were lacking. This suggests that prior to the deletion an expansion of the repeat had occured. The male patients with this deletion did not have FMR1 mRNA expression. The deceased grandfather, from whom the deletion originated, was fertile, despite the lack of FMR1 mRNA expression. This indicated that FMR1 expression is not required for spermatogenesis. Other deletions were found in 4 individual patients. These patients were mosaic for both a full mutation and a small deletion in the region surrounding the (CGG){sub n} repeat, present in approximately 5% of their cells. Sequence analysis of the regions surrounding the deletions showed that the (CGG){sub n} repeat was missing in all 4 patients. The 5{prime} endpoints of all deletions were found to be located between 75 to 53 bp proximal to the CGG repeat. This suggests a hot spot region for deletions and emphasizes the instability of this region when the CGG repeat is expanded. Models explaining the occurrence of the deletions will be discussed.

  7. Transcription-Associated R-Loop Formation across the Human FMR1 CGG-Repeat Region

    PubMed Central

    Loomis, Erick W.; Sanz, Lionel A.; Chédin, Frédéric; Hagerman, Paul J.

    2014-01-01

    Expansion of a trinucleotide (CGG) repeat element within the 5′ untranslated region (5′UTR) of the human FMR1 gene is responsible for a number of heritable disorders operating through distinct pathogenic mechanisms: gene silencing for fragile X syndrome (>200 CGG) and RNA toxic gain-of-function for FXTAS (∼55–200 CGG). Existing models have focused almost exclusively on post-transcriptional mechanisms, but co-transcriptional processes could also contribute to the molecular dysfunction of FMR1. We have observed that transcription through the GC-rich FMR1 5′UTR region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing the non-template DNA strand. Using DNA:RNA (hybrid) immunoprecipitation (DRIP) of genomic DNA from cultured human dermal fibroblasts with both normal (∼30 CGG repeats) and premutation (55<CGG<200 repeats) alleles, we provide evidence for FMR1 R-loop formation in human genomic DNA. Using a doxycycline (DOX)-inducible episomal system in which both the CGG-repeat and transcription frequency can be varied, we further show that R-loop formation increases with higher expression levels. Finally, non-denaturing bisulfite mapping of the displaced single-stranded DNA confirmed R-loop formation at the endogenous FMR1 locus and further indicated that R-loops formed over CGG repeats may be prone to structural complexities, including hairpin formation, not commonly associated with other R-loops. These observations introduce a new molecular feature of the FMR1 gene that is directly affected by CGG-repeat expansion and is likely to be involved in the associated cellular dysfunction. PMID:24743386

  8. Identification of a novel polymorphism involving a CGG repeat in the PTCH gene and a genome-wide screening of CGG-containing genes.

    PubMed

    Nagao, Kazuaki; Fujii, Katsunori; Yamada, Masao; Miyashita, Toshiyuki

    2004-01-01

    Mutations in the human homologue of the Drosophila patched gene (PTCH) are responsible for the hereditary disorder called nevoid basal cell carcinoma syndrome (NBCCS). PTCH has a CGG triplet repeat located 4 bp upstream of the first methionine codon. Here we report a novel polymorphism involving the number of the CGG-repeat. The major allele (86.3%) contained a repeat size of seven, whereas the minor allele contained eight. No significant difference in the distributions of genotypes was observed between normal and NBCCS individuals. However, when the repeat was inserted between a heterologous promoter and the luciferase gene, the longer repeats tended to induce higher luciferase activities, suggesting that the repeat length potentially affects the levels of gene expression. A genome-wide screening revealed that 68 and 146 genes contained a CGG/CCG repeat in the coding region and in the 5'-untranslated region (5'-UTR), respectively. None of the genes had this repeat in 3'-UTR. Interestingly, the number of genes with a CGG repeat in the 5'-UTR was significantly higher than that with a CCG repeat in the 5'-UTR. The localization of a CGG/CCG repeat in PTCH is quite unique in that only four other genes have been found in which the repeat is localized up to 4 bp upstream of the first methionine.

  9. CGG repeats associated with fragile X chromosome form left-handed Z-DNA structure.

    PubMed

    Renčiuk, Daniel; Kypr, Jaroslav; Vorlíčková, Michaela

    2011-03-01

    This work is a continuation of our effort to determine the structure responsible for expansion of the (CGG)(n) motif that results in fragile X chromosome syndrome. In our previous report, we demonstrated that the structure adopted by an oligonucleotide with this repeat sequence is not a quadruplex as was suggested by others. Here we demonstrate that (CGG) runs adopt another anomalous arrangement-a left-handed Z-DNA structure. The Z-DNA formation was induced by high salt and millimolar concentrations of Ni(2+) ions and likelihood of its formation increased with increasing number of repeats. In an oligonucleotide in which the CGG runs were interrupted by AGG triplets, as is observed in genomes of healthy individuals, the hairpin conformation was stabilized and Z-DNA formation was hindered. We show here that methylation of the (CGG) runs markedly stabilized Z-DNA formation. We hypothesize that rather than in the expansion process the Z-DNA may be formed by long, expanded (CGG) stretches that become hypermethylated; this would inhibit transcription resulting in disease.

  10. Targeting the r(CGG) Repeats That Cause FXTAS with Modularly Assembled Small Molecules and Oligonucleotides

    PubMed Central

    2015-01-01

    We designed small molecules that bind the structure of the RNA that causes fragile X-associated tremor ataxia syndrome (FXTAS), an incurable neuromuscular disease. FXTAS is caused by an expanded r(CGG) repeat (r(CGG)exp) that inactivates a protein regulator of alternative pre-mRNA splicing. Our designed compounds modulate r(CGG)exp toxicity in cellular models of FXTAS, and pull-down experiments confirm that they bind r(CGG)expin vivo. Importantly, compound binding does not affect translation of the downstream open reading frame (ORF). We compared molecular recognition properties of our optimal compound to oligonucleotides. Studies show that r(CGG)exp’s self-structure is a significant energetic barrier for oligonucleotide binding. A fully modified 2′-OMethyl phosphorothioate is incapable of completely reversing an FXTAS-associated splicing defect and inhibits translation of the downstream ORF, which could have deleterious effects. Taken together, these studies suggest that a small molecule that recognizes structure may be more well suited for targeting highly structured RNAs that require strand invasion by a complementary oligonucleotide. PMID:24506227

  11. Fragile X syndrome: Discordant levels of CGG repeat mosaicism in two brothers

    SciTech Connect

    Mueller, O.T.; Hartsfield, J.K. Jr.; Amar, M.J.A.

    1995-08-14

    Fragile X syndrome is associated with an unstable repeated CGG trinucleotide sequence in the 5{prime} untranslated region of the FMR-1 gene. A significant number of individuals with a mild or atypical presentation are mosaics for the CGG expansion. We report a family with two brothers. The proband had severe mental retardation as well as most of the Fragile X syndrome stigmata, whereas his brother shows only mild learning difficulties. Both inherited a 80 x CGG trinucleotide premutation from the mother. They were negative for the FRAXA fragile site in over 100 metaphases examined. Flanking markers verified that both had inherited the same FMR-1 allele and Xq27-q28 flanking sequences from the mother. The methylation status of the brothers indicated active FMR-1 transcription as determined by using StB12.3/EcoRI + Eagl blots. CGG size or methylation mosaicism was not apparent from Southern blots. Polymerase chain reaction and chemiluminescent detection identified that both brothers had different degrees of mosaicism for the CGG expansion. Large expansions amounting to 70% of the total were visible in the proband, whereas less than 5% of the signal was larger than the premutation in his mildly affected brother. These findings suggest that mosaicism may be responsible for some of the variation in penetrance in this disorder. 19 refs., 3 figs.

  12. Targeting the r(CGG) repeats that cause FXTAS with modularly assembled small molecules and oligonucleotides.

    PubMed

    Tran, Tuan; Childs-Disney, Jessica L; Liu, Biao; Guan, Lirui; Rzuczek, Suzanne; Disney, Matthew D

    2014-04-18

    We designed small molecules that bind the structure of the RNA that causes fragile X-associated tremor ataxia syndrome (FXTAS), an incurable neuromuscular disease. FXTAS is caused by an expanded r(CGG) repeat (r(CGG)(exp)) that inactivates a protein regulator of alternative pre-mRNA splicing. Our designed compounds modulate r(CGG)(exp) toxicity in cellular models of FXTAS, and pull-down experiments confirm that they bind r(CGG)(exp) in vivo. Importantly, compound binding does not affect translation of the downstream open reading frame (ORF). We compared molecular recognition properties of our optimal compound to oligonucleotides. Studies show that r(CGG)(exp)'s self-structure is a significant energetic barrier for oligonucleotide binding. A fully modified 2'-OMethyl phosphorothioate is incapable of completely reversing an FXTAS-associated splicing defect and inhibits translation of the downstream ORF, which could have deleterious effects. Taken together, these studies suggest that a small molecule that recognizes structure may be more well suited for targeting highly structured RNAs that require strand invasion by a complementary oligonucleotide.

  13. RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome.

    PubMed

    Oh, Seok Yoon; He, Fang; Krans, Amy; Frazer, Michelle; Taylor, J Paul; Paulson, Henry L; Todd, Peter K

    2015-08-01

    Fragile X-associated tremor ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG trinucleotide repeat expansion in the 5' UTR of the Fragile X gene, FMR1. FXTAS is thought to arise primarily from an RNA gain-of-function toxicity mechanism. However, recent studies demonstrate that the repeat also elicits production of a toxic polyglycine protein, FMRpolyG, via repeat-associated non-AUG (RAN)-initiated translation. Pathologically, FXTAS is characterized by ubiquitin-positive intranuclear neuronal inclusions, raising the possibility that failure of protein quality control pathways could contribute to disease pathogenesis. To test this hypothesis, we used Drosophila- and cell-based models of CGG-repeat-associated toxicity. In Drosophila, ubiquitin proteasome system (UPS) impairment led to enhancement of CGG-repeat-induced degeneration, whereas overexpression of the chaperone protein HSP70 suppressed this toxicity. In transfected mammalian cells, CGG repeat expression triggered accumulation of a UPS reporter in a length-dependent fashion. To delineate the contributions from CGG repeats as RNA from RAN translation-associated toxicity, we enhanced or impaired the production of FMRpolyG in these models. Driving expression of FMRpolyG enhanced induction of UPS impairment in cell models, while prevention of RAN translation attenuated UPS impairment in cells and suppressed the genetic interaction with UPS manipulation in Drosophila. Taken together, these findings suggest that CGG repeats induce UPS impairment at least in part through activation of RAN translation.

  14. Mutation spectra in fragile X syndrome induced by deletions of CGG*CCG repeats.

    PubMed

    Wells, Robert D

    2009-03-20

    The fragile X syndrome results from expansions as well as deletions of the repeating CGG.CCG DNA sequence in the 5'-untranslated region of the FMR1 gene on the X chromosome. The relative frequency of disease cases promoted by these two types of mutations cannot be ascertained at present because the routine clinical assay monitors only expansions. At least 30 articles have been reviewed that document the involvement of deletions of part or all of the CGG.CCG repeats along with varying extents of DNA flanking regions as well as very small mutations including single base pair changes. Studies of deletion mutants of CGG.CCG tracts in Escherichia coli plasmids revealed a similar spectrum of mutagenic products. The triplet repeat tract in a non-B conformation is the mutagen, not the sequence per se in the right-handed B helix. Hence, molecular investigations in a simple model organism may generate useful initial information toward therapeutic strategies for this disease.

  15. Single nucleotide polymorphism and FMR1 CGG repeat instability in two Basque valleys.

    PubMed

    Barasoain, Maitane; Barrenetxea, Gorka; Ortiz-Lastra, Eduardo; González, Javier; Huerta, Iratxe; Télez, Mercedes; Ramírez, Juan Manuel; Domínguez, Amaia; Gurtubay, Paula; Criado, Begoña; Arrieta, Isabel

    2012-03-01

    Fragile X Syndrome (FXS, MIM 309550) is mainly due to the expansion of a CGG trinucleotide repeat sequence, found in the 5' untranslated region of the FMR1 gene. Some studies suggest that stable markers, such as single nucleotide polymorphisms (SNPs) and the study of populations with genetic identity, could provide a distinct advance to investigate the origin of CGG repeat instability. In this study, seven SNPs (WEX28 rs17312728:G>T, WEX70 rs45631657:C>T, WEX1 rs10521868:A>C, ATL1 rs4949:A>G, FMRb rs25707:A>G, WEX17 rs12010481:C>T and WEX10 ss71651741:C>T) have been analyzed in two Basque valleys (Markina and Arratia). We examined the association between these SNPs and the CGG repeat size, the AGG interruption pattern and two microsatellite markers (FRAXAC1 and DXS548). The results suggest that in both valleys WEX28-T, WEX70-C, WEX1-C, ATL1-G, and WEX10-C are preferably associated with cis-acting sequences directly influencing instability. But comparison of the two valleys reveals also important differences with respect to: (1) frequency and structure of "susceptible" alleles and (2) association between "susceptible" alleles and STR and SNP haplotypes. These results may indicate that, in Arratia, SNP status does not identify a pool of susceptible alleles, as it does in Markina. In Arratia valley, the SNP haplotype association reveals also a potential new "protective" factor.

  16. Influence of CGG-repeat length upon FMR1 transcription and translation

    SciTech Connect

    Warren, S.T.; Zhang, F.; Lokey, L.K.

    1994-09-01

    Fragile X syndrome is the result of the expansion of a 5{prime} untranslated CGG-repeat in the FMR1 gene. In penetrant individuals the repeat is typically >230 triplets and is abnormally methylated and transcriptionally silent while premutation alleles generally contain 60-200 repeats. Consistent with the lack of penetrance among premutation carriers, FMR1 transcription and translation were found similar among normal and premutation cell lines, suggesting little influence of CGG-repeat length of <110 repeats on FMRP expression. However, similar studies of a mildly affected mosaic male with a predominantly hypomethylated allele exhibiting a mode of 300 repeats indicates an influence of larger repeats upon FMRP translation. Lymphoblasts and fibroblasts from this individual revealed normal transcription but {approximately}30% of normal FMRP levels. From an explant fibroblast culture, individual colonies were isolated and clones containing 57, 168, 182, 207, 266 and 285 hypomethylated repeats were identified. Quantitative RNase protection revealed normal steady state levels of FMR1 mRNA in these clonal cultures and RT-PCR of the repeat showed accurate transcription through the repeats. FMRP levels, quantitated using monoclonal antibody, were normal up to 182 repeats and reduced in clones containing larger repeat lengths with very little FMRP detected in the 285 repeat cells. Sucrose fractionation of ribosomes followed by RNase protection showed FMR1 mRNA associated with polyribosomes in control cells while transcripts containing 266 repeats localized predominantly to the 40-80S subunit fraction. These data indicate an inability of the ribosome to scan through lengthy trinucleotide repeats. This has implications regarding the molecular mechanisms of fragile X syndrome and other disorders due to trinucleotide repeat expansions.

  17. Stability of the FMR1 CGG repeat in a Basque sample.

    PubMed

    Arrieta, I; Gil, A; Nuñez, T; Telez, M; Martinez, B; Criado, B; Lostao, C

    1999-02-01

    The fragile X syndrome is an X-chromosome-linked dominant disorder with reduced penetrance. It is the most common inherited form of mental retardation. The molecular basis is usually the unstable expansion of a CGG trinucleotide repeat in the 5' untranslated region of the first exon of the FMR1 gene, which resides at chromosome position Xq27.3 and is coincident with the cytogenetic fragile site FRAXA, which characterizes the syndrome. In the Biscay province of the Basque Country the prevalence of FRAXA in a mentally retarded sample of non-Basque origin is in the range of other analyzed Spanish populations. In the sample of Basque origin we have not found FRAXA site expression and the repeat size is in the normal range. Based on this, we have examined FMR1 gene stability in normal individuals of Basque origin from the Biscay province. This study is based on a sample of 242 X chromosomes. The results from the CGG repeat region of FMR1 indicate that a prevalence of predisposing normal alleles toward repeat instability in the Basque population is 0.00% or near to it. This could be 1 of the explanations of the apparently low fragile X syndrome incidence found in the Basque mentally retarded sample analyzed by us. This low incidence does not seem to be associated with the flanking microsatellite markers.

  18. Absence of FMR1 protein in two mentally retarded fragile X males without CGG repeat expansion

    SciTech Connect

    Lugenbeel, K.A.; Nelson, D.L.; Carson, N.L.; Chudley, A.E.

    1994-09-01

    Fragile X syndrome is characterized by absence of the product of the FMR1 gene due to an expansion and abnormal methylation of a CGG repeat located in exon 1. While the vast majority of fragile X patients demonstrate this common mutation, a small number of non-CGG mutations have been identified among patients exhibiting features of fragile X syndrome. Three patients with large deletions ablating all or a portion of FMR1 have been previously reported. A fourth patient has been described with a point mutation resulting in an Ile367 Asn substitution. While this last individual suggests that FMR1 is directly responsible for fragile X syndrome, the severe phenotype observed suggests a gain of function mutation. Our long-term goal is to understand both the normal function of the FMR1 gene product and the consequences of its absence. Using Western blot analysis of protein extracts prepared from transformed lymphoblastoid cell lines derived from individuals suspected of fragile X syndrome without CGG expansion, we have identified two fragile X males who display no FMR1 protein. In order to facilitate identification of small-scale mutations in these patients, primers have been designed which allow amplification of each exon of the FMR1 gene along with their intron boundaries. Exons 2 through 17 of FMR1 have been analyzed by amplification of patient genomic DNA using these primers. Each patient shows normal length amplification product from each exon as assayed by agarose gel electrophoresis, suggesting the absence of insertions, deletions, or other rearrangements. Sequence analysis of exons 8, 9, 10, 11, and 12 has shown no alteration from the normal FMR1 sequence. Current analysis has focused on the use of mutation detection electrophoresis (MDE) in order to identify candidate exons for mutations. RT-PCR analysis is also under way to determine if FMR1 mRNA is present and to offer an alternative approach to mutation detection.

  19. DNA methylation and triplet repeat stability: New proposals addressing actual questions on the CGG repeat of fragile X syndrome

    SciTech Connect

    Woehrle, D.; Schwemmle, S.; Steinbach, P.

    1996-08-09

    Methylation of expanded CGG repeats in the FMR1 gene may well have different consequences. One is that methylation, extending into upstream regulatory elements, could lead to gene inactivation. Another effect of methylation, which we have obtained evidence for, could be stabilization of the repeat sequence and even prevention of premutations from expansion to full mutation. The full mutation of the fragile X syndrome probably occurs in an early transitional stage of embryonic development. The substrate is a maternally inherited premutation. The product usually is a mosaic pattern of full mutations detectable in early fetal life. These full mutation patterns are mitotically stable as, for instance, different somatic tissues of full mutation fetuses show identical mutation patterns. This raised the following questions: What triggers repeat expansion in that particular stage of development and what causes subsequent mitotic stability of expanded repeats? 21 refs., 1 fig.

  20. Cascade Screening for Fragile X Syndrome/CGG Repeat Expansions in Children Attending Special Education in Sri Lanka

    PubMed Central

    Chong, Samuel S.; Rajan-Babu, Indhu-Shree

    2015-01-01

    Fragile X syndrome (FXS) is the commonest cause of inherited mental retardation and clinically presents with learning, emotional and behaviour problems. FXS is caused by expansion of cytosine-guanine-guanine (CGG) repeats present in the 5’ untranslated region of the FMR1 gene. The aim of this study was to screen children attending special education institutions in Sri Lanka to estimate the prevalence of CGG repeat expansions. The study population comprised a representative national sample of 850 children (540 males, 310 females) with 5 to 18 years of age from moderate to severe mental retardation of wide ranging aetiology. Screening for CGG repeat expansion was carried out on DNA extracted from buccal cells using 3’ direct triplet primed PCR followed by melting curve analysis. To identify the expanded status of screened positive samples, capillary electrophoresis, methylation specific PCR and Southern hybridization were carried out using venous blood samples. Prevalence of CGG repeat expansions was 2.2%. Further classification of the positive samples into FXS full mutation, pre-mutation and grey zone gave prevalence of 1.3%, 0.8% and 0.1% respectively. All positive cases were male. No females with FXS were detected in our study may have been due to the small sample size. PMID:26694146

  1. Cascade Screening for Fragile X Syndrome/CGG Repeat Expansions in Children Attending Special Education in Sri Lanka.

    PubMed

    Chandrasekara, C H W M R Bhagya; Wijesundera, W S Sulochana; Perera, Hemamali N; Chong, Samuel S; Rajan-Babu, Indhu-Shree

    2015-01-01

    Fragile X syndrome (FXS) is the commonest cause of inherited mental retardation and clinically presents with learning, emotional and behaviour problems. FXS is caused by expansion of cytosine-guanine-guanine (CGG) repeats present in the 5' untranslated region of the FMR1 gene. The aim of this study was to screen children attending special education institutions in Sri Lanka to estimate the prevalence of CGG repeat expansions. The study population comprised a representative national sample of 850 children (540 males, 310 females) with 5 to 18 years of age from moderate to severe mental retardation of wide ranging aetiology. Screening for CGG repeat expansion was carried out on DNA extracted from buccal cells using 3' direct triplet primed PCR followed by melting curve analysis. To identify the expanded status of screened positive samples, capillary electrophoresis, methylation specific PCR and Southern hybridization were carried out using venous blood samples. Prevalence of CGG repeat expansions was 2.2%. Further classification of the positive samples into FXS full mutation, pre-mutation and grey zone gave prevalence of 1.3%, 0.8% and 0.1% respectively. All positive cases were male. No females with FXS were detected in our study may have been due to the small sample size.

  2. The frequency of different CGG-repeat alleles in the FMR-1 gene in the general population and special populations

    SciTech Connect

    Holden, J.J.A. |; Chalifoux, M.; Wing, M.

    1994-09-01

    The fragile X (FRAXA) syndrome is the most common inherited form of developmental disability and was the first genetic disorder in which the mechanism of mutation is triplet repeat expansion. The normal fragile X mental retardation-1 gene has 6-52 copies of the CGG-repeat; affected males have extensive amplification, coupled with methylation and gene inactivation; and carriers have between about 55 and 200 copies. There is some overlap in the 45-55 repeat range, with some alleles showing stable and othres unstable transmission. There have been several estimates of the incidence of the FRAXA syndrome, based on testing of special populations using chromosome analysis and the range is 1/750-1/2000. Because of the high burden associated with this syndrome, and in the face of discussions about population screening, it is important to know the actual incidence of mutations in this gene, as well as the distribution of unstable repeats above 45 copes. We have initiated a general population screening to examine 50,000 newborn samples using PCR, and have developed a rapid, inexpensive and reliable method for amplifying the CGG-repeat from Guthrie spots. In the first 1600 samples examined, we found 15 alleles with greater than 45 CGG-repeats, with the highest being 61 repeats.

  3. CGG Repeats in the 5’UTR of FMR1 RNA Regulate Translation of Other RNAs Localized in the Same RNA Granules

    PubMed Central

    Rovozzo, René; Korza, George; Baker, Mei W.; Li, Meng; Bhattacharyya, Anita; Barbarese, Elisa; Carson, John H.

    2016-01-01

    CGG repeats in the 5’UTR of Fragile X Mental Retardation 1 (FMR1) RNA mediate RNA localization and translation in granules. Large expansions of CGG repeats (> 200 repeats) in FMR1, referred to as full mutations, are associated with fragile X syndrome (FXS). Smaller expansions (55–200 repeats), referred to as premutations, are associated with fragile X tremor ataxia syndrome (FXTAS) and fragile X premature ovarian insufficiency (FXPOI). TMPyP4 is a porphyrin ring compound that destabilizes CGG repeat RNA secondary structure. Here we show that exogenous CGG repeat RNA by itself, lacking the FMRP ORF, microinjected into hippocampal neurons is localized in RNA granules and inhibits translation of ARC RNA, which is localized in the same granules. TMPyP4 rescues translation of ARC RNA in granules. We also show that in human premutation fibroblasts with endogenous CGG repeat expansions in the FMR1 gene, translation of ARC RNA is inhibited and calcium homeostasis is disrupted and both phenotypes are rescued by TMPyP4. Inhibition of granule translation by expanded CGG repeats and rescue of granule translation by TMPy4, represent potential pathogenic mechanism and therapeutic strategy, respectively, for FXTAS and FXPOI. PMID:28005950

  4. Molecular-intelligence correlations in young fragile X males with a mild CGG repeat expansion in the FMR1 gene

    SciTech Connect

    Steyaert, J.; Borghgraef, M.; Legius, E.

    1996-08-09

    Several mechanisms can explain the occurrence of full-mutation fragile X males with an IQ level above -2 SD below mean, also called {open_quotes}high-functioning fragile X males.{close_quotes} Incomplete methylation of the CpG island at the 5{prime} end of the FMR1 gene is one of these mechanisms. The present study describes the physical and behavior phenotypes in 7 fragile X boys with CGG repeat insertions in the FMR1 gene between 600-2,400 base pairs. The degree of methylation at the FMR1-associated CpG island ranges in peripheral blood lymphocytes from 0-95%. Subjects with a low degree of methylation at this site have mild or absent physical characteristics of the fragile X syndrome, while subjects with a high degree of methylation at this site have more severe physical characteristics. In this range of CGG repeat insertion (600-2,400 base pairs), the degree of methylation at the FMR1-associated CpG island is a good predictor of intelligence, while CGG repeat insertion length is not. 13 refs., 1 fig., 1 tab.

  5. Reactivation of FMR1 by CRISPR/Cas9-Mediated Deletion of the Expanded CGG-Repeat of the Fragile X Chromosome

    PubMed Central

    Xie, Nina; Gong, He; Suhl, Joshua A.; Chopra, Pankaj; Wang, Tao

    2016-01-01

    Fragile X syndrome (FXS) is a common cause of intellectual disability that is most often due to a CGG-repeat expansion mutation in the FMR1 gene that triggers epigenetic gene silencing. Epigenetic modifying drugs can only transiently and modestly induce FMR1 reactivation in the presence of the elongated CGG repeat. As a proof-of-principle, we excised the expanded CGG-repeat in both somatic cell hybrids containing the human fragile X chromosome and human FXS iPS cells using the CRISPR/Cas9 genome editing. We observed transcriptional reactivation in approximately 67% of the CRISPR cut hybrid colonies and in 20% of isolated human FXS iPSC colonies. The reactivated cells produced FMRP and exhibited a decline in DNA methylation at the FMR1 locus. These data demonstrate the excision of the expanded CGG-repeat from the fragile X chromosome can result in FMR1 reactivation. PMID:27768763

  6. Reactivation of FMR1 by CRISPR/Cas9-Mediated Deletion of the Expanded CGG-Repeat of the Fragile X Chromosome.

    PubMed

    Xie, Nina; Gong, He; Suhl, Joshua A; Chopra, Pankaj; Wang, Tao; Warren, Stephen T

    2016-01-01

    Fragile X syndrome (FXS) is a common cause of intellectual disability that is most often due to a CGG-repeat expansion mutation in the FMR1 gene that triggers epigenetic gene silencing. Epigenetic modifying drugs can only transiently and modestly induce FMR1 reactivation in the presence of the elongated CGG repeat. As a proof-of-principle, we excised the expanded CGG-repeat in both somatic cell hybrids containing the human fragile X chromosome and human FXS iPS cells using the CRISPR/Cas9 genome editing. We observed transcriptional reactivation in approximately 67% of the CRISPR cut hybrid colonies and in 20% of isolated human FXS iPSC colonies. The reactivated cells produced FMRP and exhibited a decline in DNA methylation at the FMR1 locus. These data demonstrate the excision of the expanded CGG-repeat from the fragile X chromosome can result in FMR1 reactivation.

  7. Sequestration of DROSHA and DGCR8 by Expanded CGG RNA Repeats Alters MicroRNA Processing in Fragile X-Associated Tremor/Ataxia Syndrome

    PubMed Central

    Sellier, Chantal; Freyermuth, Fernande; Tabet, Ricardos; Tran, Tuan; He, Fang; Ruffenach, Frank; Alunni, Violaine; Moine, Herve; Thibault, Christelle; Page, Adeline; Tassone, Flora; Willemsen, Rob; Disney, Matthew D.; Hagerman, Paul J.; Todd, Peter K.; Charlet-Berguerand, Nicolas

    2013-01-01

    SUMMARY Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder caused by the expansion of 55–200 CGG repeats in the 5′ UTR of FMR1. These expanded CGG repeats are transcribed and accumulate in nuclear RNA aggregates that sequester one or more RNA-binding proteins, thus impairing their functions. Here, we have identified that the double-stranded RNA-binding protein DGCR8 binds to expanded CGG repeats, resulting in the partial sequestration of DGCR8 and its partner, DROSHA, within CGG RNA aggregates. Consequently, the processing of micro-RNAs (miRNAs) is reduced, resulting in decreased levels of mature miRNAs in neuronal cells expressing expanded CGG repeats and in brain tissue from patients with FXTAS. Finally, overexpression of DGCR8 rescues the neuronal cell death induced by expression of expanded CGG repeats. These results support a model in which a human neurodegenerative disease originates from the alteration, in trans, of the miRNA-processing machinery. PMID:23478018

  8. Decrease in the CGG{sub n} trinucleotide repeat mutation of the fragile X syndrome to normal size range during paternal transmission

    SciTech Connect

    Vaeisaenen, M.L.; Haataja, R.; Leisti, J.

    1996-09-01

    The fragile X syndrome, the most common inherited form of mental retardation, is caused by the expansion of a CGG{sub n} trinucleotide repeat in the FMR-1 gene. Although the repeat number usually increases during transmission, few cases with reduction of an expanded CGG{sub n} repeat back to the normal size range have been reported. We describe for the first time a family in which such reduction has occurred in the paternal transmission. The paternal premutation ({Delta} = 300 hp) was not detected in one of the five daughters or in the son of this daughter, although he had the grandpaternal RFLP haplotype. Instead, fragments indicating the normal CGG{sub n} repeat size were seen on a Southern blot probed with StB12.3. PCR analysis of the CGG{sub n} repeat confirmed this; in addition to a maternal allele of 30 repeats, an allele of 34 repeats was detected in the daughter and, further, in her son. Sequencing of this new allele revealed a pure CGG{sub n} repeat configuration without AGG interruptions. No evidence for a somatic mosaicism of a premutation allele in the daughter or a normal allele in her father was detected when investigating DNA derived from blood lymphocytes and skin fibroblasts. Another unusual finding in this family was lack of the PCR product of the microsatellite marker RS46 (DXS548) in one of the grandmaternal X chromosomes, detected as incompatible inheritance of RS46 alleles. The results suggest an intergenerational reduction in the CGG{sub n} repeat from premutation size to the normal size range and stable transmission of the contracted repeat to the next generation. However, paternal germ-line mosaicism could not be excluded as an alternative explanation for the reverse mutation. 37 refs., 4 figs.

  9. FMR1 CGG repeat distribution and linked microsatellite-SNP haplotypes in normal Mexican Mestizo and indigenous populations.

    PubMed

    Felix-López, Xóchitl Adriana; Argüello-García, Raúl; Cerda-Flores, Ricardo M; Peñaloza-Espinoza, Rosenda I; Buentello-Malo, Leonor; Estrada-Mena, Francisco Javier; Ramos-Kuri, Manuel; Gómez, Fabio Salamanca; Arenas-Aranda, Diego Julio

    2006-10-01

    The (CGG)n repeat size distribution in the FMR1 gene was studied in healthy individuals: 80 X chromosomes of Mexican Mestizos from Mexico City and 33 X chromosomes of Mexican Amerindians from three indigenous communities (Purepechas, Nahuas, and Tzeltales), along with alleles and haplotypes defined by two microsatellite polymorphic markers (DXS548 and FRAXAC1) and two single nucleotide polymorphisms (FMRA and FMRB). Genetic frequencies of Mestizo and Amerindian subpopulations were statistically similar in almost all cases and thus were considered one population for comparisons with other populations. Sixteen (CGG)n alleles in the 17-38 size range were observed, and the most common were the 25 (38.0%), 26 (28.3%), and 24 (12.3%) repeat alleles. This pattern differs from most other populations reported, but a closer relation to Amerindian, European, and African populations was found, as expected from the historical admixture that gave rise to Mexican Mestizos. The results of the CA repeats analysis at DXS548-FRAXAC1 were restricted to nine haplotypes, of which haplotypes 7-4 (52.2%), 8-4 (23.8%), and 7-3 (11.5%) were predominant. The modal haplotype 7-4, instead of the nearly universal haplotype 7-3, had been reported exclusively in Eastern Asian populations. Likewise, only seven different FRAXAC1-FMRA-FMRB haplotypes were observed, including five novel haplotypes (3TA, 4TA, 3 - A, 4 - A, and 5 - A), compared with Caucasians. Of these, haplotypes - A (78.7%) and 3 - A (13.2%) were the most common in the Mexican population. These data suggest a singular but relatively low genetic diversity at FMR1 in the studied Mexican populations that may be related to the recent origin of Mestizos and the low admixture rate of Amerindians.

  10. The structural basis of actinomycin D–binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats

    PubMed Central

    Lo, Yu-Sheng; Tseng, Wen-Hsuan; Chuang, Chien-Ying; Hou, Ming-Hon

    2013-01-01

    The potent anticancer drug actinomycin D (ActD) functions by intercalating into DNA at GpC sites, thereby interrupting essential biological processes including replication and transcription. Certain neurological diseases are correlated with the expansion of (CGG)n trinucleotide sequences, which contain many contiguous GpC sites separated by a single G:G mispair. To characterize the binding of ActD to CGG triplet repeat sequences, the structural basis for the strong binding of ActD to neighbouring GpC sites flanking a G:G mismatch has been determined based on the crystal structure of ActD bound to ATGCGGCAT, which contains a CGG triplet sequence. The binding of ActD molecules to GCGGC causes many unexpected conformational changes including nucleotide flipping out, a sharp bend and a left-handed twist in the DNA helix via a two site-binding model. Heat denaturation, circular dichroism and surface plasmon resonance analyses showed that adjacent GpC sequences flanking a G:G mismatch are preferred ActD-binding sites. In addition, ActD was shown to bind the hairpin conformation of (CGG)16 in a pairwise combination and with greater stability than that of other DNA intercalators. Our results provide evidence of a possible biological consequence of ActD binding to CGG triplet repeat sequences. PMID:23408860

  11. Instability of the CGG repeat at the FRAXA locus and variable phenotypic expression in a large fragile X pedigree.

    PubMed Central

    Pintado, E; de Diego, Y; Hmadcha, A; Carrasco, M; Sierra, J; Lucas, M

    1995-01-01

    Fragile X syndrome is the major cause of inherited mental retardation. The molecular basis for the expression of the fragile X phenotype is the expansion of an unstable CGG repeat element which inhibits transcription of the FMR1 gene. The fragile X syndrome shows great diversity in its phenotype as well as in its cytogenetic and molecular status. We have studied, in a large fragile X family, the correlation between the molecular data and the phenotypic expression of the syndrome. We report two brothers who carry identical unmethylated premutated alleles but present different clinical phenotypes. We also suggest that reductions in allele size from one generation to another may be, as in other diseases, because of triplet amplifications, more common at the FRAXA locus than previously thought. Images PMID:8592340

  12. Expansion of the CGG repeat in fragile X in the FRM1 gene depends on the sex of the offspring

    SciTech Connect

    Loesch, D.Z.; Huggins, R.; Petrovic, V.

    1995-12-01

    Analysis of 139 mother-to-offspring transmissions of fragile X CGG triplet repeats revealed that the repeat expansion is enhanced in mother-to-son transmissions compared with mother-to-daughter transmissions. Evidence has been based on analysis of mother-offspring differences in the size of repeat (in kb), as well as on comparisons between proportions of male and female offspring with premutations, and full mutations, inherited from mothers carrying a premutation. Mean difference in the repeat size from mother-son transmissions was 1.45 kb, compared with mother-daughter transmissions of 0.76 kb. The difference is due primarily to a greater proportion of male than female offspring with full mutation from the premutation mothers and also to a higher frequency of reduction in repeat size from mothers to daughters than from mothers to sons. Our findings suggest the possibility of an interaction of the normal X homologue in a female zygote with the FMR1 sequence on the fragile X during replication to account for the lower level of expansion in mother-to-daughter transmissions relative to mother-to-son transmissions. 27 refs., 3 figs., 2 tabs.

  13. Unusual mutations in high functioning fragile X males: apparent instability of expanded unmethylated CGG repeats.

    PubMed Central

    Wöhrle, D; Salat, U; Gläser, D; Mücke, J; Meisel-Stosiek, M; Schindler, D; Vogel, W; Steinbach, P

    1998-01-01

    We report on further cases of high functioning fragile X males showing decreased expression of FMR1 protein, absence of detectable methylation at the EagI site in the FMR1 gene promoter, and highly unusual patterns of fragile X mutations defined as smear of expansions extending from premutation to full mutation range. Very diffuse and therefore not easily detectable patterns of full mutations were also observed on prenatal testing using DNA from chorionic villi sampled at a time of development when full mutations were still unmethylated in this particular tissue. In the search for possible determinants of such unusual patterns, repeat expansions in the premutation and in the lower full mutation range were identified on genomic PstI blots previously prepared for fragile X DNA testing. Cases with 130 or more triplets, and a number of shorter repeats, were reinvestigated on EcoRI plus EagI digests. Among the 119 expansions, there were 22 in our sample showing either blurred bands or smears on PstI blots. This particular characteristic was strongly associated with the coincidence of a repeat size of more than 130 triplets and absence of EagI site methylation. Our data set also includes cases of mosaic patterns consisting of smears of unmethylated expansions to more than 130 CGGs and of clear bands of methylated expansions. We therefore suggest that in fragile X syndrome unusual smeared patterns of mutations result from somatic instability of larger repeats under circumstantial absence of repeat methylation. Images PMID:9507388

  14. Instability of the CGG repeat and expression of the FMRI protein in a male fragile X patient with a lung tumor

    SciTech Connect

    Graaff, E. de; Willemsen, R.; Zhong, N.

    1995-09-01

    The molecular mechanism of the fragile X syndrome is based on the expansion of an CGG repeat in the 5{prime} UTR of the FMR1 gene in the majority of fragile X patients. This repeat displays instability both between individuals and within an individual. We studied the instability of the CGG repeat and the expression of the FMR1 protein (FMRP) in several different tissues derived from a male fragile X patient. Using Southern blot analysis, only a full mutation is detected in 9 of the 11 tissues tested. The lung tumor contains a methylated premutation of 160 repeats, whereas in the testis, besides the full mutation, a premutation of 60 CGG repeats is detected. Immunohistochemistry of the testis revealed expression of FMR1 in the spermatogonia only, confirming the previous finding that, in the sperm cells of fragile X patients with a full mutation in their blood cells, only a premutation is present. Immunohistochemistry of brain and lung tissue revealed that 1% of the cells are expressing the FMRP. PCR analysis demonstrated the presence of a premutation of 160 repeats in these FMR1-expressing cells. This indicates that the tumor was derived from a lung cell containing a premutation. Remarkably, despite the methylation of the EagI and BssHII sites, FMRP expression is detected in the tumor. Methylation of both restriction sites has thus far resulted in a 100% correlation with the lack of FMR1 expression, but the results found in the tumor suggest that the CpGs in these restriction sites are not essential for regulation of FMR1 expression. This indicates a need for a more accurate study of the exact promoter of FMR1. 54 refs., 4 figs.

  15. A CGG-repeat expansion mutation in ZNF713 causes FRA7A: association with autistic spectrum disorder in two families.

    PubMed

    Metsu, Sofie; Rainger, Jacqueline K; Debacker, Kim; Bernhard, Birgitta; Rooms, Liesbeth; Grafodatskaya, Daria; Weksberg, Rosanna; Fombonne, Eric; Taylor, Martin S; Scherer, Stephen W; Kooy, R Frank; FitzPatrick, David R

    2014-11-01

    We report de novo occurrence of the 7p11.2 folate-sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG-repeat expansion mutation (∼450 repeats) in a 5' intron of ZNF713. This expanded allele showed hypermethylation of the adjacent CpG island with reduced ZNF713 expression observed in a proband-derived lymphoblastoid cell line (LCL). His unaffected mother carried an unmethylated premutation (85 repeats). This CGG-repeat showed length polymorphism in control samples (five to 22 repeats). In a second unrelated family, three siblings with ASD and their unaffected father were found to carry FRA7A premutations, which were partially or mosaically methylated. In one of the affected siblings, mitotic instability of the premutation was observed. ZNF713 expression in LCLs in this family was increased in three of these four premutation carriers. A firm link cannot yet be established between ASD and the repeat expansion mutation but plausible pathogenic mechanisms are discussed.

  16. Validation of a commercially available test that enables the quantification of the numbers of CGG trinucleotide repeat expansion in FMR1 gene.

    PubMed

    Lim, Grace X Y; Yeo, Minli; Koh, Yvonne Y; Winarni, Tri Indah; Rajan-Babu, Indhu-Shree; Chong, Samuel S; Faradz, Sultana M H; Guan, Ming

    2017-01-01

    In the present study, we evaluated a commercially available TP-PCR-based assay, the FastFraXTM FMR1 Sizing kit, as a test in quantifying the number of CGG repeats in the FMR1 gene. Based on testing with well characterized DNA samples from Coriell, the kit yielded size results within 3 repeats of those obtained by common consensus (n = 14), with the exception of one allele. Furthermore, based on data obtained using all Coriell samples with or without common consensus (n = 29), the Sizing kit was 97.5% in agreement with existing approaches. Additionally, the kit generated consistent size information in repeatability and reproducibility studies (CV 0.39% to 3.42%). Clinical performance was established with 198 archived clinical samples, yielding results of 100% sensitivity (95% CI, 91.03% to 100%) and 100% specificity (95% CI, 97.64% to 100%) in categorizing patient samples into the respective normal, intermediate, premutation and full mutation genotypes.

  17. Validation of a commercially available test that enables the quantification of the numbers of CGG trinucleotide repeat expansion in FMR1 gene

    PubMed Central

    Yeo, Minli; Koh, Yvonne Y.; Winarni, Tri Indah; Rajan-Babu, Indhu-Shree; Chong, Samuel S.; Faradz, Sultana M. H.; Guan, Ming

    2017-01-01

    In the present study, we evaluated a commercially available TP-PCR-based assay, the FastFraXTM FMR1 Sizing kit, as a test in quantifying the number of CGG repeats in the FMR1 gene. Based on testing with well characterized DNA samples from Coriell, the kit yielded size results within 3 repeats of those obtained by common consensus (n = 14), with the exception of one allele. Furthermore, based on data obtained using all Coriell samples with or without common consensus (n = 29), the Sizing kit was 97.5% in agreement with existing approaches. Additionally, the kit generated consistent size information in repeatability and reproducibility studies (CV 0.39% to 3.42%). Clinical performance was established with 198 archived clinical samples, yielding results of 100% sensitivity (95% CI, 91.03% to 100%) and 100% specificity (95% CI, 97.64% to 100%) in categorizing patient samples into the respective normal, intermediate, premutation and full mutation genotypes. PMID:28278294

  18. Normal number of CGG repeats in the FMR-1 gene and abnormal incorporation of fibrillin into the extracellular matrix in Lujan Syndrome

    SciTech Connect

    Greenhaw, G.A.; Stone, C.; Milewicz, D.

    1994-09-01

    Lujan syndrome is an X-linked condition that includes mild-to-moderate mental retardation, poor social integration, normal secondary sexual development with normal testicular size, generalized hypotonia, hypernasal voice and dolichostenomelia. Major cardiac complications and lens dislocation have not been reported although severe myopia may occur. All reported cases have had negative cytogenetic screening for fra(X) syndrome but establishing this constellation of findings as a distinctive entity has been difficult. We report 4 males in two sibships with clinical findings consistent with Lujan syndrome, normal karyotypes, negative cytogenetic screening for fra(X) syndrome and a normal number of CGG repeats in the FMR-1 gene. Dermal fibroblasts explanted from one of the affected males were used to study fibrillin synthesis secretion and extracellular matrix incorporation into microfibrils. Cells from the affected individual showed normal synthesis and secretion of fibrillin when compared to control cells, but the fibrillin was not incorporated into the extracellular matrix. These results suggest the presence of a gene on the X chromosome which may play a role in microfibril assembly and when deficient may disrupt the incorporation of fibrillin into microfibrils. This may be important not only in normal body morphogenesis but also in the development/function of the brain. More affected individuals are needed to investigate these findings further.

  19. A fragile X male with a broad smear on southern blot analysis representing 100-500 CGG repeats and no methylation at the EagI site of the FMR-1 gene

    SciTech Connect

    Lachiewicz, A.M.; Spiridigliozzi, G.A.; McConkie-Rosell, A.

    1996-08-09

    Fragile X DNA studies were carried out on all obligate carriers of a large fragile X family with 10 mentally retarded individuals. One 64-year-old carrier man with an altered FMR-1 allele was not described as being mentally retarded or as having any limitations in function. He was married, raised 8 children, and worked as an auto mechanic. On examination, he had macrocephaly and mild macroorchidism but few of the other typical physical findings of males with fragile X syndrome. His Full Scale IQ is 73, and his Vineland Adaptive Behavior Composite is 73. On the Woodcock-Johnson Psycho-Educational Battery-Revised, he achieved standard scores of 64 in Reading, 55 in Math, and 83 in Knowledge. His DNA findings showed a broad smear on Southern blot analysis of 100-500 CGG repeats and no methylation at the EagI site upstream of the FMR-1 protein coding region. His FMR-1 protein production is 12% of normal. His daughters all have large premutations, with somatic instability in the size of the CGG repeat lengths. They all have evidence of academic underachievement and 2 have physical characteristics frequently described in individuals with fragile X. 21 refs., 3 figs.

  20. Retrotransposon activation contributes to fragile X premutation rCGG-mediated neurodegeneration

    PubMed Central

    Tan, Huiping; Qurashi, Abrar; Poidevin, Mickael; Nelson, David L.; Li, He; Jin, Peng

    2012-01-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with fragile X premutation carriers. Previous studies have shown that fragile X rCGG repeats are sufficient to cause neurodegeneration and that the rCGG-repeat-binding proteins Pur α and heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 could modulate rCGG-mediated neuronal toxicity. Mobile genetic elements or their remnants populate the genomes, and the activities of these elements are tightly controlled for the fitness of host genomes in different organisms. Here we provide both biochemical and genetic evidence to show that the activation of a specific retrotransposon, gypsy, can modulate rCGG-mediated neurodegeneration in an FXTAS Drosophila model. We find that one of the rCGG-repeat-binding proteins, hnRNP A2/B1, is involved in this process via interaction with heterochromatin protein 1. Knockdown of gypsy RNA by RNAi could suppress the neuronal toxicity caused by rCGG repeats. These data together point to a surprisingly active role for retrotransposition in neurodegeneration. PMID:21940752

  1. A Small Molecule that Targets r(CGG)exp and Improves Defects in Fragile X-Associated Tremor Ataxia Syndrome

    PubMed Central

    Disney, Matthew D.; Liu, Biao; Yang, Wang-Yong; Sellier, Chantal; Tran, Tuan; Charlet-Berguerand, Nicolas; Childs-Disney, Jessica L.

    2012-01-01

    The development of small molecule chemical probes or therapeutics that target RNA remains a significant challenge despite the great interest in such compounds. The most significant barrier to compound development is a lack of knowledge of the chemical and RNA motif spaces that interact specifically. Herein, we describe a bioactive small molecule probe that targets expanded r(CGG) repeats, or r(CGG)exp , that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5’CGG/3’GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp -protein complex in vitro. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition to r(CGG)exp . Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)exp -protein aggregates. This approach may establish a general strategy to identify lead ligands that target RNA while also providing a chemical probe to dissect the varied mechanisms by which r(CGG)exp promotes toxicity. PMID:22948243

  2. A small molecule that targets r(CGG)(exp) and improves defects in fragile X-associated tremor ataxia syndrome.

    PubMed

    Disney, Matthew D; Liu, Biao; Yang, Wang-Yong; Sellier, Chantal; Tran, Tuan; Charlet-Berguerand, Nicolas; Childs-Disney, Jessica L

    2012-10-19

    The development of small molecule chemical probes or therapeutics that target RNA remains a significant challenge despite the great interest in such compounds. The most significant barrier to compound development is defining which chemical and RNA motif spaces interact specifically. Herein, we describe a bioactive small molecule probe that targets expanded r(CGG) repeats, or r(CGG)(exp), that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium binds the 5'CGG/3'GGC motifs in r(CGG)(exp) and disrupts a toxic r(CGG)(exp)-protein complex in vitro. Structure-activity relationship studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG)(exp). Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)(exp)-containing nuclear foci. This approach may establish a general strategy to identify lead ligands that target RNA while also providing a chemical probe to dissect the varied mechanisms by which r(CGG)(exp) promotes toxicity.

  3. Small Molecule Recognition and Tools to Study Modulation of r(CGG)(exp) in Fragile X-Associated Tremor Ataxia Syndrome.

    PubMed

    Yang, Wang-Yong; He, Fang; Strack, Rita L; Oh, Seok Yoon; Frazer, Michelle; Jaffrey, Samie R; Todd, Peter K; Disney, Matthew D

    2016-09-16

    RNA transcripts containing expanded nucleotide repeats cause many incurable diseases via various mechanisms. One such disorder, fragile X-associated tremor ataxia syndrome (FXTAS), is caused by a noncoding r(CGG) repeat expansion (r(CGG)(exp)) that (i) sequesters proteins involved in RNA metabolism in nuclear foci, causing dysregulation of alternative pre-mRNA splicing, and (ii) undergoes repeat associated non-ATG translation (RANT), which produces toxic homopolymeric proteins without using a start codon. Here, we describe the design of two small molecules that inhibit both modes of toxicity and the implementation of various tools to study perturbation of these cellular events. Competitive Chemical Cross Linking and Isolation by Pull Down (C-Chem-CLIP) established that compounds bind r(CGG)(exp) and defined small molecule occupancy of r(CGG)(exp) in cells, the first approach to do so. Using an RNA GFP mimic, r(CGG)(exp)-Spinach2, we observe that our optimal designed compound binds r(CGG)(exp) and affects RNA localization by disrupting preformed RNA foci. These events correlate with an improvement of pre-mRNA splicing defects caused by RNA gain of function. In addition, the compounds reduced levels of toxic homopolymeric proteins formed via RANT. Polysome profiling studies showed that small molecules decreased loading of polysomes onto r(CGG)(exp), explaining decreased translation.

  4. Fragile X syndrome and the (CGG)[sub n] mutation: Two families with discordant MZ twins

    SciTech Connect

    Kruyer, H.; Estivill, X.; Mila, M.; Ballesta, F.; Glover, G.; Carbonell, P. )

    1994-03-01

    The fragile X phenotype has been found, in the majority of cases, to be due to the expansion of a CGG repeat in the 5'UTR region of the FMR-1 gene, accompanied by methylation of the adjacent CpG island and inactivation of the FMR-1 gene. Although several important aspects of genetics of fragile X have been resolved, it remains to be elucidated at which stage in development the transition from the premutation to the full mutation occurs. The authors present two families in which discordance between two sets of MZ twins illustrates two important genetic points. In one family, two affected MZ brothers differed in the number of CGG repeats, demonstrating in vivo mitotic instability of this CGG repeat and suggesting that the transition to the full mutation occurred postzygotically. In the second family, two MZ sisters had the same number of repeats, but only one was mentally retarded. When the methylation status of the FMR-1 CpG island was studied, the authors found that the majority of normal chromosomes had been inactivated in the affected twin, thus leading to the expression of the fragile X phenotype. 29 refs., 3 figs., 1 tab.

  5. Repeat-mediated epigenetic dysregulation of the FMR1 gene in the fragile X-related disorders.

    PubMed

    Usdin, Karen; Kumari, Daman

    2015-01-01

    The fragile X-related disorders are members of the Repeat Expansion Diseases, a group of genetic conditions resulting from an expansion in the size of a tandem repeat tract at a specific genetic locus. The repeat responsible for disease pathology in the fragile X-related disorders is CGG/CCG and the repeat tract is located in the 5' UTR of the FMR1 gene, whose protein product FMRP, is important for the proper translation of dendritic mRNAs in response to synaptic activation. There are two different pathological FMR1 allele classes that are distinguished only by the number of repeats. Premutation alleles have 55-200 repeats and confer risk of fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Full mutation alleles on the other hand have >200 repeats and result in fragile X syndrome, a disorder that affects learning and behavior. Different symptoms are seen in carriers of premutation and full mutation alleles because the repeat number has paradoxical effects on gene expression: Epigenetic changes increase transcription from premutation alleles and decrease transcription from full mutation alleles. This review will cover what is currently known about the mechanisms responsible for these changes in FMR1 expression and how they may relate to other Repeat Expansion Diseases that also show repeat-mediated changes in gene expression.

  6. Analysis of FMR1 (CGG)(n) alleles and DXS548-FRAXAC1 haplotypes in three European circumpolar populations: traces of genetic relationship with Asia.

    PubMed

    Larsen, L A; Vuust, J; Nystad, M; Evseeva, I; Van Ghelue, M; Tranebjaerg, L

    2001-09-01

    Fragile X syndrome, the most common form of inherited mental retardation, is caused by expansion of a (CGG)(n) repeat located in the FMR1 gene. The molecular factors involved in the mutation process from stable (CGG)(n) alleles towards unstable alleles are largely unknown, although family transmission studies and population studies have suggested that loss of AGG interruptions in the (CGG)(n) repeat is essential. We have analysed the AGG interspersion pattern of the FMR1 (CGG)(n) repeat and the haplotype distribution of closely located microsatellite markers DXS548 and FRAXAC1, in three circumarctic populations: Norwegians, Nenets and Saami. The data confirm the conservation, reported in all human populations studied so far, of an AGG interruption for each 9-10 CGG and support the stabilising effect of AGG interruptions. The data also indicate the existence of chromosomes of Asian origin in the Saami and Nenets population, thereby confirming a genetic relationship between Northern Europe and Asia. DXS548-FRAXAC1 haplotype frequencies were compared between 24 Norwegian fragile X males and 119 normal males. Significant linkage disequilibrium were found between the fragile X mutation and haplotype 6-4 and between normal (CGG)(n) alleles and haplotype 7-3.

  7. Promoter-Bound Trinucleotide Repeat mRNA Drives Epigenetic Silencing in Fragile X Syndrome

    PubMed Central

    Colak, Dilek; Zaninovic, Nikica; Cohen, Michael S.; Rosenwaks, Zev; Yang, Wang-Yong; Gerhardt, Jeannine; Disney, Matthew D.; Jaffrey, Samie R.

    2015-01-01

    Epigenetic gene silencing is seen in several repeat-expansion diseases. In fragile X syndrome, the most common genetic form of mental retardation, a CGG trinucleotide–repeat expansion adjacent to the fragile X mental retardation 1 (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1 silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5′ untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA·DNA duplex. Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1 gene prevents promoter silencing. Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA. PMID:24578575

  8. Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome.

    PubMed

    Colak, Dilek; Zaninovic, Nikica; Cohen, Michael S; Rosenwaks, Zev; Yang, Wang-Yong; Gerhardt, Jeannine; Disney, Matthew D; Jaffrey, Samie R

    2014-02-28

    Epigenetic gene silencing is seen in several repeat-expansion diseases. In fragile X syndrome, the most common genetic form of mental retardation, a CGG trinucleotide-repeat expansion adjacent to the fragile X mental retardation 1 (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1 silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5' untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA·DNA duplex. Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1 gene prevents promoter silencing. Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA.

  9. Evidence for high-risk haplotypes and (CGG)n expansion in fragile X syndrome in the Hellenic population of Greece and Cyprus

    SciTech Connect

    Syrrou, M.; Georgiou, I.; Pagoulatos, G.

    1996-07-12

    The expansion of the trinucleotide repeat (CGG){sub n} in successive generations through maternal meiosis is the cause of fragile X syndrome. Analysis of CA repeat polymorphisms flanking the FMR-1 gene provides evidence of a limited number of {open_quotes}founder{close_quotes} chromosomes and predisposing high-risk haplotypes related to the mutation. To investigate the origin of mutations in the fragile X syndrome in the Hellenic populations of Greece and Cyprus, we studied the alleles and haplotypes at DXS548 and FRAXAC2 loci of 16 independent fragile X and 70 normal control chromosomes. In addition, we studied 191 unrelated normal X chromosomes for the distribution and frequencies of CGG alleles. At DXS548, 6 alleles were found, 2 (194 and 196) of which were represented on fragile X chromosomes. At FRAXAC2, 6 alleles were found, 4 of which were present on fragile X chromosomes. Sixteen haplotypes were identified, but only 5 were present on fragile X chromosomes. The highest number of CGG repeats ({ge} 33) were associated with haplotypes 194-147, 194-151, 194-153, and 204-155. The data provide evidence for founder chromosomes and high-risk haplotypes in the Hellenic population. 20 refs., 3 figs., 2 tabs.

  10. Unusual (CGG)n expansion and recombination in a family with fragile X and DiGeorge syndrome.

    PubMed

    Macpherson, J N; Curtis, G; Crolla, J A; Dennis, N; Migeon, B; Grewal, P K; Hirst, M C; Davies, K E; Jacobs, P A

    1995-03-01

    In a fragile X family referred for prenatal diagnosis, the female fetus did not inherit the full fragile X mutation from her mother, but an unexpected expansion within the normal range of CGG repeats from 29 to 39 was observed in the paternal X chromosome. Also, a rare recombination between DXS548 and FRAXAC1 was recorded in the maternal meiosis. Follow up of the neonate confirmed the same DNA genotype as in the CVS, but the child died of DiGeorge syndrome after four days and was subsequently found to carry a microdeletion of chromosome 22 using probe cEO. It is suggested that in this family the deletion of chromosome 22 is likely to be a chance event but the rare recombinant and the fragile X mutation might be causally related.

  11. Determination of the Canadian Gravimetric Geoid 2005 (CGG05) Using GRACE and Terrestrial Gravity Data

    NASA Astrophysics Data System (ADS)

    Huang, J.; Véronneau, M.

    2005-12-01

    The remove-restore technique and the Stokes kernel modification allow the combination of satellite gravity models and terrestrial gravity data for the determination of regional/continental high-resolution gravimetric geoid models. A number of kernel modifications have been suggested over the years to minimize errors in the satellite models and terrestrial data. However, the selection of the proper modification to the Stokes kernel depends largely on data quality. The Vanicek and Kleusberg (VK) kernel provides an efficient way to reduce the far-zone contribution (or truncation) error in the case of poor satellite models and poor remote (far zone) terrestrial gravity data. On the other hand, the degree-banded kernel acts as a filter weight function to remove systematic errors in the long wavelength components of the terrestrial gravity anomalies. It places significant emphasis on the satellite model. Back in 2000, the VK kernel and EGM96 were used in determining the Canadian Gravimetric Geoid 2000 (CGG2000). The kernel was modified to degree 30 to prevent error accumulation from EGM96. The validation of CGG2000 at 430 precise GPS-leveling stations indicates a standard deviation of 21.7 cm. Today, the GRACE mission is advancing the determination of the Earth gravity field to a new level. It poses a compelling question: What is the proper approach to combine GRACE models and the terrestrial gravity data? This presentation investigates methods of combining the high-accuracy of the GRACE gravity models with the high precision of the terrestrial gravity data for optimal estimation of the long- and short-wavelength components of the geoid model. First, a series of numerical simulations are conducted to study the effect of systematic and random errors in the satellite and terrestrial data on geoid modeling. Second, geoid models for North America are estimated from the GRACE gravity model (GGM02C) and terrestrial gravity data using different combination approaches. The

  12. On the formation of nucleosomes within the FMR1 trinucleotide repeat

    SciTech Connect

    Metzenberg, S.

    1996-07-01

    Zhong et al. presented an intriguing analysis both of the AGG trinucleotides interspersed in the CGG/CCG triplet repeats of the FMR1 gene and of the effect that they may have no trinucleotide-repeat expansion. They suggested that pure FMR1 triplet repeats >50 repeats in length might efficiently form nucleosomes, promoting trinucleotide-repeat expansion through strand slippage or a pause during DNA replication. Several recent papers suggest, however, that the free energy of nucleosome formation on DNA consisting of only guanylate and cytidylate nucleotides is extremely unfavorable, because of the inflexibility of the DNA. Expanded CGG/CCG trinucleotide repeats may therefore repress rather than encourage nucleosome formation, and the DNA decondensation and {open_quotes}fragile{close_quotes} chromosome aberration may be a direct consequence of the thermodynamics of DNA bending. 6 refs., 1 fig.

  13. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

    ERIC Educational Resources Information Center

    Hagerman, Paul J.; Hagerman, Randi J.

    2004-01-01

    Carriers of fragile X mental retardation 1 ("FMR1") premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (greater than 200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55-200 repeats) develop a neurological syndrome…

  14. Isolation and characterization of human brain genes with (CCA){sub n} trinucleotide repeats

    SciTech Connect

    Longshore, J.W.; Finley, W.H.; Descartes, M.

    1994-09-01

    Expansion of trinucleotide repeats has been described as a new form of mutation. To date, only the expansion of (CGG){sub n} and (CAG){sub n} repeats have been associated with disease. Expansion of (CAG){sub n} repeats has been found to cause Huntington`s disease, Kennedy`s disease, myotonic dystrophy, spinocerebellar ataxia type 1, and dentatorubral pallidoluysian atrophy. (CGG){sub n} repeat expansion has been implicated in the fragile X syndrome and FRAXE mental retardation. In an effort to identify other potential repeats as candidates for expansion, a DNA linguistics approach was used to study 10 Mb of human DNA sequences in GenBank. Our study found the (CCA){sub n} repeat and the disease-associated (CGG){sub n} and (CAG){sub n} repeats to be over-represented in the human genome. The (CCA){sub n} repeat also shares other characteristics with (CGG){sub n} and (CAG){sub n}, making it a good candidate for expansion. Trinucleotide repeat numbers in disease-associated genes are normally polymorphic in a population. Therefore, by studying genes for polymorphisms, candidate genes may be identified. Twelve sequences previously deposited in GenBank with at least five tandem copies of (CCA) were studied and no polymorphisms were found. To identify other candidate genes, a human hippocampus cDNA library was screened with a (CCA){sub 8} probe. This approach identified 19 novel expressed sequences having long tandem (CCA){sub n} repeats which are currently under investigation for polymorphisms. Genes with polymorphic repeats may serve as markers for linkage studies or as candidate genes for genetic diseases showing anticipation.

  15. The puzzle of the triple repeats

    SciTech Connect

    Morell, V.

    1993-06-04

    Two years ago, when researchers discovered the gene that causes a hereditary form of mental retardation known as fragile-X syndrome, they also turned up a mutation so unexpected geneticists are still scratching their heads over it. The defect, which makes genes balloon in size by adding extra copies of a three base-pair repeated sequence of DNA, was the first of its kind. Despite decades of study, nothing like it had ever been seen in any of the species that laid the foundations for modern genetics: bacteria, the fruit fly Drosophila melanogaster, and the mouse. The mutations caused by these expanding trinucleotide repeats turned out be common causes of human disease. In the past 2 years, they have been fingered as the culprits in three hereditary disorders besides fragile-X syndrome: myotronic dystrophy, spinobullar muscular atrophy (also known as Kennedy's disease), and just this March-Huntington's disease. The FMR-1 gene, which is the one at fault in fragile-X syndrome, shows just how much the trinucleotide repeats can expand. The normal gene carries at most 50 copies of the CGG trinucleotide. But in children who inherit the gene from these carriers and actually develop mental retardation and the other fragile-X symptoms, the FMR-1 gene may have hundreds to thousands of CGG repeats. Huge expansions of another trinucleotide repeat (CTG) can also occur from one generation to the next in the gene that causes myotonic dystrophy (DM), while smaller, although no less devastating, expansions in the CAG trinucleotide repeat lead to Huntington's and Kennedy's diseases.

  16. Sequence analysis of the fragile X trinucleotide repeat: Correlations with stability and haplotype and implications for the origin of fragile X alleles

    SciTech Connect

    Snow, K.; Tester, D.J.; Kruckeberg, K.E.; Thibodeau, S.N.

    1994-09-01

    Fragile X (FX) syndrome is associated with amplification of a CGG trinucleotide repeat in the 5{prime} untranslated region of the gene FMR-1. To address mechanism of instability and concern related to overlap between sizes of normal stable alleles and FX unstable alleles, we have sequenced 165 alleles to analyze patterns of AGG interruptions within the CGG repeat, and have typed the (CA)n at DXS548 for 204 chromosomes. Overall, our data is consistent with the idea that the length of uninterrupted CGG repeats determines instability. For 17 stably transmitted alleles with total repeat lengths between 33 and 51, the longest stretch of uninterrupted CGGs was 41. In contrast, for 13 premutation alleles, the shortest stretch of uninterrupted CGGs was 48, suggesting a threshold for expansion between 41 and 48 pure CGGs. For expansion from a premutation to a full mutation, the threshold appears to be {ge}70 uninterrupted repeats. Interestingly, an AGG was detected in some carriers of a full mutation. Comparison of the number of {open_quote}shadow bands{close_quote} in PCR products from similar size alleles with different AGG interruption patterns supports replication slippage as a potential mechanism, i.e. replication slippage occurs more readily as the length of pure repeat increases. Alleles with high total repeat lengths but up to 3 AGGs may be relatively protected against expansion, whereas smaller alleles with pure CGG sequence could be at higher risk for instability. Comparison of sequence data and DXS548 (CA)n data revealed specific sequence trends for each of the DXS548 alleles, explaining the previously reported haplotype association with FX. Incorporating these observations into models for the origin of FX alleles, we consider replication slippage, unequal crossover within the CGG repeat region, recombination between FMR-1 and DXS548, and loss of AGGs by A to C transversion.

  17. Recognition of hypermethylated triplet repeats in vitro by cationic nanoparticles

    NASA Astrophysics Data System (ADS)

    Gearheart, Latha A.; Caswell, Kimberlyn; Murphy, Catherine J.

    2001-04-01

    Genomic DNA contains many higher-order structural deviations from the Watson-Crick global average. The massive expansion and hypermethylation of the duplex triplet repeat (CCG)n(CGG)n has characteristic higher-order structures that are associated with the fragile X syndrome. We have used luminescent mineral nanoparticles of protein-sized cadmium sulfide in optical assays to detect anomalous DNA structures. The photoluminescence of these particles is sensitive to the presence and nature of adsorbates. We previously found that our nanoparticles bind the fragile X repeat well but do not bind to normal double-helical DNA. In this study, we have determined that these particles are also able to detect the hypermethylated forms of these triplet repeats. Therefore, these nanoparticles may form the basis for future optical assays of higher-order DNA structures, especially those associated with human disease.

  18. Extended gene diversity at the FMR1 locus and neighbouring CA repeats in a sub-Saharan population

    SciTech Connect

    Chiurazzi, Genuardi, M.; Neri, G.

    1996-07-12

    We report on the allele distributions in a normal black African population at two microsatellite loci neighbouring the FRAXA locus and at the CGG repeat in the 5{prime} end of the FMR1 gene, which causes the fragile X syndrome. The CGG repeat distribution was found to be similar to that of other ethnic groups, as well as to that of other non-human primates, possibly predicting a comparable prevalence of fragile X in Africa. Significant linkage disequilibrium has been observed between fragile X mutations and alleles of the DXS548 and FRAXAC1 loci in European and Asian populations, and some founder chromosomes may be extremely old. Those associated with FRAXAC1-A and DXS548-2 alleles are not present in the Asian fragile X samples. We searched for these alleles and their frequency in the well defined Bamileke population of Cameroon. All previously described alleles and some new ones were found in this sample, supporting the hypothesis of their pre-existence and subsequent loss in Asian populations. Finally, the heterozygosity of the Bamileke sample was significantly higher at both marker loci and comparable to that of Europeans at the CGG repeat, confirming the notion that genetic diversity is greater in Africans than in other groups and supporting the view that evolution of modern man started in Africa. 31 refs., 1 fig., 1 tab.

  19. Bidirectional transcription of trinucleotide repeats: roles for excision repair

    PubMed Central

    Budworth, Helen; McMurray, Cynthia T.

    2013-01-01

    SUMMARY Genomic instability at repetitive DNA regions in cells of the nervous system leads to a number of neurodegenerative and neuromuscular diseases, including those with an expanded trinucleotide repeat (TNR) tract at or nearby an expressed gene. Expansion causes disease when a particular base sequence is repeated beyond the normal range, interfering with the expression or properties of a gene product. Disease severity and onset depend on the number of repeats. As the length of the repeat tract grows, so does the size of the successive expansions and the likelihood of another unstable event. In fragile X syndrome, for example, CGG repeat instability and pathogenesis are not typically observed below tracts of roughly 50 repeats, but occur frequently at or above 55 repeats, and are virtually certain above 100–300 repeats. Recent evidence points to bidirectional transcription as a new aspect of TNR instability and pathophysiology. Bidirectional transcription of TNR genes produces novel proteins and/or regulatory RNAs that influence both toxicity and epigenetic changes in TNR promoters. Bidirectional transcription of the TNR tract appears to influence aspects of its stability, gene processing, splicing, gene silencing, and chemical modification of DNAs. Paradoxically, however, some of the same effects are observed on both the expanded TNR gene and on its normal gene counterpart. In this review, we discuss the possible normal and abnormal effects of bidirectional transcription on trinucleotide repeat instability, the role of DNA repair in causing, preventing, or maintaining methylation, and chromatin environment of TNR genes. PMID:23669397

  20. Repeated nightmares

    MedlinePlus

    ... different from night terrors . Alternative Names Nightmares - repeated; Dream anxiety disorder References American Academy of Family Physicians. Information from your family doctor. Nightmares and night terrors in children. ...

  1. Disease-associated repeat instability and mismatch repair.

    PubMed

    Schmidt, Monika H M; Pearson, Christopher E

    2016-02-01

    Expanded tandem repeat sequences in DNA are associated with at least 40 human genetic neurological, neurodegenerative, and neuromuscular diseases. Repeat expansion can occur during parent-to-offspring transmission, and arise at variable rates in specific tissues throughout the life of an affected individual. Since the ongoing somatic repeat expansions can affect disease age-of-onset, severity, and progression, targeting somatic expansion holds potential as a therapeutic target. Thus, understanding the factors that regulate this mutation is crucial. DNA repair, in particular mismatch repair (MMR), is the major driving force of disease-associated repeat expansions. In contrast to its anti-mutagenic roles, mammalian MMR curiously drives the expansion mutations of disease-associated (CAG)·(CTG) repeats. Recent advances have broadened our knowledge of both the MMR proteins involved in disease repeat expansions, including: MSH2, MSH3, MSH6, MLH1, PMS2, and MLH3, as well as the types of repeats affected by MMR, now including: (CAG)·(CTG), (CGG)·(CCG), and (GAA)·(TTC) repeats. Mutagenic slipped-DNA structures have been detected in patient tissues, and the size of the slip-out and their junction conformation can determine the involvement of MMR. Furthermore, the formation of other unusual DNA and R-loop structures is proposed to play a key role in MMR-mediated instability. A complex correlation is emerging between tissues showing varying amounts of repeat instability and MMR expression levels. Notably, naturally occurring polymorphic variants of DNA repair genes can have dramatic effects upon the levels of repeat instability, which may explain the variation in disease age-of-onset, progression and severity. An increasing grasp of these factors holds prognostic and therapeutic potential.

  2. Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target

    PubMed Central

    Krzyzosiak, Wlodzimierz J.; Sobczak, Krzysztof; Wojciechowska, Marzena; Fiszer, Agnieszka; Mykowska, Agnieszka; Kozlowski, Piotr

    2012-01-01

    This review presents detailed information about the structure of triplet repeat RNA and addresses the simple sequence repeats of normal and expanded lengths in the context of the physiological and pathogenic roles played in human cells. First, we discuss the occurrence and frequency of various trinucleotide repeats in transcripts and classify them according to the propensity to form RNA structures of different architectures and stabilities. We show that repeats capable of forming hairpin structures are overrepresented in exons, which implies that they may have important functions. We further describe long triplet repeat RNA as a pathogenic agent by presenting human neurological diseases caused by triplet repeat expansions in which mutant RNA gains a toxic function. Prominent examples of these diseases include myotonic dystrophy type 1 and fragile X-associated tremor ataxia syndrome, which are triggered by mutant CUG and CGG repeats, respectively. In addition, we discuss RNA-mediated pathogenesis in polyglutamine disorders such as Huntington's disease and spinocerebellar ataxia type 3, in which expanded CAG repeats may act as an auxiliary toxic agent. Finally, triplet repeat RNA is presented as a therapeutic target. We describe various concepts and approaches aimed at the selective inhibition of mutant transcript activity in experimental therapies developed for repeat-associated diseases. PMID:21908410

  3. Ups and Downs: Mechanisms of Repeat Instability in the Fragile X-Related Disorders

    PubMed Central

    Zhao, Xiao-Nan; Usdin, Karen

    2016-01-01

    The Fragile X-related disorders (FXDs) are a group of clinical conditions resulting from the expansion of a CGG/CCG-repeat tract in exon 1 of the Fragile X mental retardation 1 (FMR1) gene. While expansions of the repeat tract predominate, contractions are also seen with the net result being that individuals can show extensive repeat length heterogeneity in different tissues. The mechanisms responsible for expansion and contraction are still not well understood. This review will discuss what is known about these processes and current evidence that supports a model in which expansion arises from the interaction of components of the base excision repair, mismatch repair and transcription coupled repair pathways. PMID:27657135

  4. Trinucleotide repeat expansion in the FRAXE locus is not common among institutionalized individuals with non-specific developmental disabilities

    SciTech Connect

    Holden, J.J.A.; Julien-Inalsingh, C.; Fidler, K.

    1996-08-09

    Expansion of a polymorphic GCC-repeat at the FRAXE locus has been associated with expression of chromosome fragility at this site and cognitive impairment in some individuals previously testing negative for CGG-repeat expansion in the fragile X mental retardation-1 (FMR1) gene. To determine the frequency of FRAXE triplet repeat expansion among persons with developmental disability, 396 individuals from two institutions were studied, all of whom were negative for FMR1 repeat expansion. Clinically, there was a wide range of mental impairment, with the majority (61.1%) being severely to profoundly affected. The distribution of FRAXE GCC-repeat numbers in the study population was 5-38:28 (5.6%) with 10-14 repeats; 366 (73.8%) with 15-19 repeats; 74 (14.9%) with 20-24 repeats; 20 (4.0%) with 25-29 repeats; and 5 (1.0%) with 30-38 repeats, with no individuals demonstrating repeat expansion. One profoundly retarded male was found to have a deletion of about 40 bp. Southern blots of HindIII-digested DNAs from individuals with {ge}26 repeats all showed normal patterns. These results suggest that FRAXE GCC-repeat expansion is not a common cause of developmental disability in institutionalized persons with mild to profound mental retardation. 15 refs., 1 fig., 2 tabs.

  5. In situ optical sequencing and structure analysis of a trinucleotide repeat genome region by localization microscopy after specific COMBO-FISH nano-probing

    NASA Astrophysics Data System (ADS)

    Stuhlmüller, M.; Schwarz-Finsterle, J.; Fey, E.; Lux, J.; Bach, M.; Cremer, C.; Hinderhofer, K.; Hausmann, M.; Hildenbrand, G.

    2015-10-01

    Trinucleotide repeat expansions (like (CGG)n) of chromatin in the genome of cell nuclei can cause neurological disorders such as for example the Fragile-X syndrome. Until now the mechanisms are not clearly understood as to how these expansions develop during cell proliferation. Therefore in situ investigations of chromatin structures on the nanoscale are required to better understand supra-molecular mechanisms on the single cell level. By super-resolution localization microscopy (Spectral Position Determination Microscopy; SPDM) in combination with nano-probing using COMBO-FISH (COMBinatorial Oligonucleotide FISH), novel insights into the nano-architecture of the genome will become possible. The native spatial structure of trinucleotide repeat expansion genome regions was analysed and optical sequencing of repetitive units was performed within 3D-conserved nuclei using SPDM after COMBO-FISH. We analysed a (CGG)n-expansion region inside the 5' untranslated region of the FMR1 gene. The number of CGG repeats for a full mutation causing the Fragile-X syndrome was found and also verified by Southern blot. The FMR1 promotor region was similarly condensed like a centromeric region whereas the arrangement of the probes labelling the expansion region seemed to indicate a loop-like nano-structure. These results for the first time demonstrate that in situ chromatin structure measurements on the nanoscale are feasible. Due to further methodological progress it will become possible to estimate the state of trinucleotide repeat mutations in detail and to determine the associated chromatin strand structural changes on the single cell level. In general, the application of the described approach to any genome region will lead to new insights into genome nano-architecture and open new avenues for understanding mechanisms and their relevance in the development of heredity diseases.

  6. The chicken FMR1 gene is highly conserved with a CCT 5{prime} - untranslated repeat and encodes an RNA-binding protein

    SciTech Connect

    Price, D.K.; Zhang, F.; Ashley, C.T. Jr.; Warren, S.T.

    1996-01-01

    The transcriptional silencing of the human gene, fragile X metal retardation 1 (FMR1), is due to abnormal methylation in response to an expanded 5{prime}-untranslated CGG trinucleotide repeat and accounts for most cases of fragile X syndrome, a frequent inherited form of metal retardation. Although the encoded fragile X mental retardation protein (FMRP) is known to have properties of a RNA-binding protein, the precise function of FMRP remains to be elucidated. We report the cloning of the chicken homolog of FMR1 and show strong evolutionary conservation, with nucleotide and amino acid identities of 85 and 92%, respectively, between chicken and human. In place of the mammalian CGG trinucleotide repeat, a 99-nt tripartite repetitive element containing a CCT trinucleotide repeat flanked on both sides by dinucleotide repeats was identified. Blocks of highly conserved 3{prime}-untranslated sequence were also found. Within the coding region, two copies each of the highly conserved K homology motif and the Arg-Gly-Gly (RGG) box motif, both ribonucleotide particle family domains implicated in RNA binding, were identified. Chicken FMRP was found to bind RNA in vitro, and this activity correlated with the presence of the carboxy-terminal portion of the protein that includes the RGG motifs. 49 refs., 7 figs.

  7. Study of the Genetic Etiology of Primary Ovarian Insufficiency: FMR1 Gene.

    PubMed

    Barasoain, Maitane; Barrenetxea, Gorka; Huerta, Iratxe; Télez, Mercedes; Criado, Begoña; Arrieta, Isabel

    2016-12-13

    Menopause is a period of women's life characterized by the cessation of menses in a definitive way. The mean age for menopause is approximately 51 years. Primary ovarian insufficiency (POI) refers to ovarian dysfunction defined as irregular menses and elevated gonadotrophin levels before or at the age of 40 years. The etiology of POI is unknown but several genes have been reported as being of significance. The fragile X mental retardation 1 gene (FMR1) is one of the most important genes associated with POI. The FMR1 gene contains a highly polymorphic CGG repeat in the 5' untranslated region of exon 1. Four allelic forms have been defined with respect to CGG repeat length and instability during transmission. Normal (5-44 CGG) alleles are usually transmitted from parent to offspring in a stable manner. The full mutation form consists of over 200 repeats, which induces hypermethylation of the FMR1 gene promoter and the subsequent silencing of the gene, associated with Fragile X Syndrome (FXS). Finally, FMR1 intermediate (45-54 CGG) and premutation (55-200 CGG) alleles have been principally associated with two phenotypes, fragile X tremor ataxia syndrome (FXTAS) and fragile X primary ovarian insufficiency (FXPOI).

  8. [Carriers of fragile X syndrome can present with a broad spectrum of clinical disorders].

    PubMed

    Jønch, Aia Elise; Grønskov, Karen; Carlsen Lunding, Jytte Merete; Nielsen, Jørgen E; Brøndum-Nielsen, Karen

    2014-06-23

    Fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) are three clinically distinct disorders caused by expansions of a CGG repeat sequence in the non-coding part of the FMR1. FXTAS and FXPOI are seen in carriers of smaller repeat expansions (55-200). Carriers were for many years thought to be clinically unaffected, but along with the discovery of FXPOI and FXTAS a growing number of additional clinical manifestations have been identified. We wish to make Danish physicians more aware of these conditions which we review in this paper.

  9. Cis-acting DNA sequence at a replication origin promotes repeat expansion to fragile X full mutation

    PubMed Central

    Zaninovic, Nikica; Zhan, Qiansheng; Madireddy, Advaitha; Nolin, Sarah L.; Ersalesi, Nicole; Yan, Zi; Rosenwaks, Zev

    2014-01-01

    Fragile X syndrome (FXS) is caused by CGG repeat expansion that leads to FMR1 silencing. Women with a premutation allele are at risk of having a full mutation child with FXS. To investigate the mechanism of repeat expansion, we examined the relationship between a single-nucleotide polymorphism (SNP) variant that is linked to repeat expansion in haplogroup D and a replication origin located ∼53 kb upstream of the repeats. This origin is absent in FXS human embryonic stem cells (hESCs), which have the SNP variant C, but present in the nonaffected hESCs, which have a T variant. The SNP maps directly within the replication origin. Interestingly, premutation hESCs have a replication origin and the T variant similar to nonaffected hESCs. These results suggest that a T/C SNP located at a replication origin could contribute to the inactivation of this replication origin in FXS hESCs, leading to altered replication fork progression through the repeats, which could result in repeat expansion to the FXS full mutation. PMID:25179629

  10. 2D and 3D FISH of expanded repeat RNAs in human lymphoblasts.

    PubMed

    Urbanek, Martyna O; Michalak, Michał; Krzyzosiak, Wlodzimierz J

    2017-04-09

    The first methods for visualizing RNAs within cells were designed for simple imaging of specific transcripts in cells or tissues and since then significant technical advances have been made in this field. Today, high-resolution images can be obtained, enabling visualization of single transcript molecules, quantitative analyses of images, and precise localization of RNAs within cells as well as co-localization of transcripts with specific proteins or other molecules. In addition, tracking of RNA dynamics within single cell has become possible. RNA imaging techniques have been utilized for investigating the role of mutant RNAs in a number of human disorders caused by simple microsattelite expansions. These diseases include myotonic dystrophy type 1 and 2, amyotrophic lateral sclerosis/frontotemporal dementia, fragile X-associated tremor/ataxia syndrome, and Huntington's disease. Mutant RNAs with expanded repeats tend to aggregate predominantly within cell nuclei, forming structures called RNA foci. In this study, we demonstrate methods for fluorescent visualization of RNAs in both fixed and living cells using the example of RNAs containing various expanded repeat tracts (CUG, CCUG, GGGGCC, CGG, and CAG) from experiment design to image analysis. We describe in detail 2D and 3D fluorescence in situ hybridization (FISH) protocols for imaging expanded repeats RNAs, and we review briefly live imaging techniques used to characterize RNA foci formed by mutant RNAs. These methods could be used to image the entire cellular pathway of RNAs, from transcription to degradation.

  11. Conversion disorder in women with the FMR1 premutation.

    PubMed

    Seritan, Andreea L; Schneider, Andrea; Olichney, John M; Leehey, Maureen A; Akins, R Scott; Hagerman, Randi J

    2009-11-01

    Women with fragile X mental retardation (FMR1) gene premutations (55-200 CGG repeats) were until recently believed to be unaffected. It is now known that up to 8% of older female FMR1 premutation carriers develop fragile X-associated tremor/ataxia syndrome (FXTAS). Female carriers may also develop primary ovarian insufficiency, thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia. We present a 60-year-old woman with FMR1 premutation who had depression, anxiety, and conversion disorder with seizures. The FMR1 premutation with its associated mRNA toxicity is postulated as an underlying neurobiological mechanism of conversion symptoms, through functional and structural neural dysconnectivity.

  12. FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile.

    PubMed

    Santa María, Lorena; Aliaga, Solange; Faundes, Víctor; Morales, Paulina; Pugin, Ángela; Curotto, Bianca; Soto, Paula; Peña, M Ignacia; Salas, Isabel; Alliende, M Angélica

    2016-06-28

    Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and co-morbid autism. It is caused by an amplification of the CGG repeat (>200), which is known as the full mutation, within the 5'UTR of the FMR1 gene. Expansions between 55-200 CGG repeats are termed premutation and are associated with a greater risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated premature ovarian insufficiency. Intermediate alleles, also called the grey zone, include approximately 45-54 repeats and are considered borderline. Individuals with less than 45 repeats have a normal FMR1 gene. We report the occurrence of CGG expansions of the FMR1 gene in Chile among patients with ID and families with a known history of FXS. Here, we present a retrospective review conducted on 2321 cases (2202 probands and 119 relatives) referred for FXS diagnosis and cascade screening at the Institute of Nutrition and Food Technology (INTA), University of Chile. Samples were analysed using traditional cytogenetic methods and/or PCR. Southern blot was used to confirm the diagnosis. Overall frequency of FMR1 expansions observed among probands was 194 (8·8%), the average age of diagnosis was 8·8 ± 5·4 years. Of 119 family members studied, 72 (60%) were diagnosed with a CGG expansion. Our results indicated that the prevalence of CGG expansions of the FMR1 gene among probands is relatively higher than other populations. The average age of diagnosis is also higher than reference values. PCR and Southern blot represent a reliable molecular technique in the diagnosis of FXS.

  13. Repeating the Past

    NASA Astrophysics Data System (ADS)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  14. Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders.

    PubMed

    Usdin, Karen; Hayward, Bruce E; Kumari, Daman; Lokanga, Rachel A; Sciascia, Nicholas; Zhao, Xiao-Nan

    2014-01-01

    The Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor/ataxia syndrome (FXTAS), the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI) and the intellectual disability, Fragile X syndrome (FXS). The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5' UTR of the Fragile X mental retardation 1 (FMR1) gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, Fragile X mental retardation 1 protein (FMRP). Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by an FMRP deficiency, the clinical picture is turning out to be more complex than once appreciated. Added complications result from the fact that increasing repeat numbers make the alleles somatically unstable. Thus many individuals have a complex mixture of different sized alleles in different cells. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects.

  15. Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders

    PubMed Central

    Usdin, Karen; Hayward, Bruce E.; Kumari, Daman; Lokanga, Rachel A.; Sciascia, Nicholas; Zhao, Xiao-Nan

    2014-01-01

    The Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor/ataxia syndrome (FXTAS), the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI) and the intellectual disability, Fragile X syndrome (FXS). The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5′ UTR of the Fragile X mental retardation 1 (FMR1) gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, Fragile X mental retardation 1 protein (FMRP). Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by an FMRP deficiency, the clinical picture is turning out to be more complex than once appreciated. Added complications result from the fact that increasing repeat numbers make the alleles somatically unstable. Thus many individuals have a complex mixture of different sized alleles in different cells. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects. PMID:25101111

  16. Duct Leakage Repeatability Testing

    SciTech Connect

    Walker, Iain; Sherman, Max

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  17. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

  18. Duct Leakage Repeatability Testing

    SciTech Connect

    Walker, Iain; Sherman, Max

    2014-08-01

    The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

  19. A superfolding Spinach2 reveals the dynamic nature of trinucleotide repeat RNA

    PubMed Central

    Strack, Rita L.; Disney, Matthew D.; Jaffrey, Samie R.

    2013-01-01

    Fluorescent imaging of RNA in living cells is a technically challenging problem in cell biology. One strategy for genetically encoding fluorescent RNAs is to express them as fusions with ‘RNA mimics of GFP’. These are short aptamer tags that exhibit fluorescence upon binding otherwise nonfluorescent fluorophores that resemble those found in GFP. We find that the brightest of these aptamers, Spinach, often exhibits reduced fluorescence after it is fused to RNAs of interest. We show that a combination of thermal instability and a propensity for misfolding account for the low fluorescence of various Spinach-RNA fusions. Using systematic mutagenesis, we identified nucleotides that account for the poor folding of Spinach, and generated Spinach2, which exhibits markedly improved thermal stability and folding in cells. Furthermore, we show that Spinach2 largely retains its fluorescence when fused to various RNAs. Using Spinach2, we detail the cellular dynamics of the CGG trinucleotide-repeat containing “toxic RNA” associated with Fragile-X tremor/ataxia syndrome, and show that these RNAs form nuclear foci with unexpected morphological plasticity that is regulated by the cell cycle and by small molecules. Together, these data demonstrate that Spinach2 exhibits improved versatility for fluorescently labeling RNAs in living cells. PMID:24162923

  20. Repeat Customer Success in Extension

    ERIC Educational Resources Information Center

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  1. 78 FR 65594 - Vehicular Repeaters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ... changes, and on whether current mobile repeater filter technologies can support reduced frequency... feasibility of adapting SAW filters, or other filter technology, for mobile repeater use. We particularly... mobile repeaters by public safety licensees on certain frequencies in the VHF band. DATES:...

  2. Altered neural activity of magnitude estimation processing in adults with the fragile X premutation.

    PubMed

    Kim, So-Yeon; Hashimoto, Ryu-ichiro; Tassone, Flora; Simon, Tony J; Rivera, Susan M

    2013-12-01

    Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Expanded CGG trinucleotide repeat (>200 repeats) result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA, and are associated with the risk of developing a neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). While impairments in numerical processing have been well documented in FXS, recent behavioral research suggests that premutation carriers also present with subtle but significant impairments in numerical processing. Using fMRI, the current study examined whether asymptomatic adults with the premutation would show aberrant neural correlates of magnitude estimation processing in the fronto-parietal area. Using a magnitude estimation task, we demonstrated that activity in the intraparietal sulcus and inferior frontal gyrus, associated with magnitude estimation processing, was significantly attenuated in premutation carriers compared to their neurotypical counterparts despite their comparable behavioral performance. Further, multiple regression analysis using CGG repeat size and FMR1 mRNA indicated that increased CGG repeat size is a primary factor for the decreased fronto-parietal activity, suggesting that reduced FMRP, rather than a toxic gain-of-function effect from elevated mRNA, contributes to altered neural activity of magnitude estimation processing in premutation carriers. In conclusion, we provide the first evidence on the aberrant neural correlates of magnitude estimation processing in premutation carriers accounted for by their FMR1 gene expression.

  3. RepeatsDB: a database of tandem repeat protein structures

    PubMed Central

    Di Domenico, Tomás; Potenza, Emilio; Walsh, Ian; Gonzalo Parra, R.; Giollo, Manuel; Minervini, Giovanni; Piovesan, Damiano; Ihsan, Awais; Ferrari, Carlo; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2014-01-01

    RepeatsDB (http://repeatsdb.bio.unipd.it/) is a database of annotated tandem repeat protein structures. Tandem repeats pose a difficult problem for the analysis of protein structures, as the underlying sequence can be highly degenerate. Several repeat types haven been studied over the years, but their annotation was done in a case-by-case basis, thus making large-scale analysis difficult. We developed RepeatsDB to fill this gap. Using state-of-the-art repeat detection methods and manual curation, we systematically annotated the Protein Data Bank, predicting 10 745 repeat structures. In all, 2797 structures were classified according to a recently proposed classification schema, which was expanded to accommodate new findings. In addition, detailed annotations were performed in a subset of 321 proteins. These annotations feature information on start and end positions for the repeat regions and units. RepeatsDB is an ongoing effort to systematically classify and annotate structural protein repeats in a consistent way. It provides users with the possibility to access and download high-quality datasets either interactively or programmatically through web services. PMID:24311564

  4. To Repeat or Not to Repeat a Course

    ERIC Educational Resources Information Center

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  5. Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes

    SciTech Connect

    Oudet, C.; Lentes-Zengerling, S.; Kretz, C.; Mandel, J.L. ); Mornet, E.; Thomas, F.; Deluchat, C.; Boue, J.; Boue, A. ); Serre, J.L. INSERM U155, Paris ); Tejada, I. )

    1993-02-01

    In order to investigate the origin of mutations responsible for the fragile X syndrome, two polymorphic CA repeats, one at 10 kb (FRAXAC2) and the other at 150 kb (DXS548) from the mutation target, were analyzed in normal and fragil X chromosomes. Contrary to observations made in myotonic dystrophy, fragil X mutations were not strongly associated with a single allele at the marker loci. However, significant differences in allelic and haplotypic distributions were observed between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. The authors propose a putative scheme with six founder chromosomes from which most of the observed fragile X-linked haplotypes can be derived directly or by a single event at one of the marker loci, either a change of one repeat unit or a recombination between DXS548 and the mutation target. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen. 23 refs., 2 figs., 3 tabs.

  6. Nifty Nines and Repeating Decimals

    ERIC Educational Resources Information Center

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  7. All-photonic quantum repeaters

    NASA Astrophysics Data System (ADS)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-04-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories.

  8. Quantum repeaters: fundamental and future

    NASA Astrophysics Data System (ADS)

    Li, Yue; Hua, Sha; Liu, Yu; Ye, Jun; Zhou, Quan

    2007-04-01

    An overview of the Quantum Repeater techniques based on Entanglement Distillation and Swapping is provided. Beginning with a brief history and the basic concepts of the quantum repeaters, the article primarily focuses on the communication model based on the quantum repeater techniques, which mainly consists of two fundamental modules --- the Entanglement Distillation module and the Swapping module. The realizations of Entanglement Distillation are discussed, including the Bernstein's Procrustean method, the Entanglement Concentration and the CNOT-purification method, etc. The schemes of implementing Swapping, which include the Swapping based on Bell-state measurement and the Swapping in Cavity QED, are also introduced. Then a comparison between these realizations and evaluations on them are presented. At last, the article discusses the experimental schemes of quantum repeaters at present, documents some remaining problems and emerging trends in this field.

  9. Repeatability in redundant manipulator systems

    NASA Astrophysics Data System (ADS)

    Mukherjee, Ranjan

    1994-02-01

    Terrestrial manipulators with more DOF than the dimension of the workspace and space manipulators with as many manipulator DOF as the dimension of the workspace are both redundant systems. An interesting problem of such redundant systems has been the repeatability problem due to the presence of nonholonomic constraints. We show, contrary to the existing belief, that integrability of the nonholonomic constraints is not a necessary condition for the repeatability of the configuration variables. There exist certain trajectories in the independent configuration variable space that are like 'holonomic loops' along which the redundant manipulators exhibit repeatable motion. We present a simple method based on optimization techniques for designing repeatable trajectories for free-flying space manipulators and terrestrial manipulators under pseudoinverse control.

  10. Protein Repeats from First Principles.

    PubMed

    Turjanski, Pablo; Parra, R Gonzalo; Espada, Rocío; Becher, Verónica; Ferreiro, Diego U

    2016-04-05

    Some natural proteins display recurrent structural patterns. Despite being highly similar at the tertiary structure level, repeating patterns within a single repeat protein can be extremely variable at the sequence level. We use a mathematical definition of a repetition and investigate the occurrences of these in sequences of different protein families. We found that long stretches of perfect repetitions are infrequent in individual natural proteins, even for those which are known to fold into structures of recurrent structural motifs. We found that natural repeat proteins are indeed repetitive in their families, exhibiting abundant stretches of 6 amino acids or longer that are perfect repetitions in the reference family. We provide a systematic quantification for this repetitiveness. We show that this form of repetitiveness is not exclusive of repeat proteins, but also occurs in globular domains. A by-product of this work is a fast quantification of the likelihood of a protein to belong to a family.

  11. Protein Repeats from First Principles

    PubMed Central

    Turjanski, Pablo; Parra, R. Gonzalo; Espada, Rocío; Becher, Verónica; Ferreiro, Diego U.

    2016-01-01

    Some natural proteins display recurrent structural patterns. Despite being highly similar at the tertiary structure level, repeating patterns within a single repeat protein can be extremely variable at the sequence level. We use a mathematical definition of a repetition and investigate the occurrences of these in sequences of different protein families. We found that long stretches of perfect repetitions are infrequent in individual natural proteins, even for those which are known to fold into structures of recurrent structural motifs. We found that natural repeat proteins are indeed repetitive in their families, exhibiting abundant stretches of 6 amino acids or longer that are perfect repetitions in the reference family. We provide a systematic quantification for this repetitiveness. We show that this form of repetitiveness is not exclusive of repeat proteins, but also occurs in globular domains. A by-product of this work is a fast quantification of the likelihood of a protein to belong to a family. PMID:27044676

  12. Conformational properties of DNA dodecamers containing four tandem repeats of the CNG triplets.

    PubMed Central

    Vorlícková, M; Zimulová, M; Kovanda, J; Fojtík, P; Kypr, J

    1998-01-01

    We studied DNA dodecamers (CAG)4, (CCG)4, (CGG)4 and (CTG)4by CD spectroscopy and polyacrylamide gel electrophoresis. Each dodecamer adopted several ordered conformers which denatured in a cooperative way. Stability of the conformers depended on the dodecamer concentration, ionic strength, temperature and pH. The dodecamers, having a pyrimidine base in the triplet center, generated foldbacks at low ionic strength whose stem conformations were governed by the GC pairs. At high salt, (CCG)4 isomerized into a peculiar association of two strands. The association was also promoted by high oligonucleotide concentrations. No similar behavior was exhibited by (CTG)4. At low salt, (CGG)4 coexisted in two bimolecular conformers whose populations were strongly dependent on the ionic strength. In addition, (CGG)4 associated into a tetraplex at acidic pH. A tetraplex was even observed at neutral pH if the (CGG)4 concentration was sufficiently high. (CAG)4 was very stable in a monomolecular conformer similar to the known extremely stable foldback of the (GCGAAGC) heptamer. Nevertheless, even this very stable conformer disappeared if (CTG)4 was added to the solution of (CAG)4. Association of the complementary strands was also strongly preferred to the particular strand conformations by the other couple, (CCG)4 and (CGG)4. PMID:9592154

  13. Nanospring behaviour of ankyrin repeats.

    PubMed

    Lee, Gwangrog; Abdi, Khadar; Jiang, Yong; Michaely, Peter; Bennett, Vann; Marszalek, Piotr E

    2006-03-09

    Ankyrin repeats are an amino-acid motif believed to function in protein recognition; they are present in tandem copies in diverse proteins in nearly all phyla. Ankyrin repeats contain antiparallel alpha-helices that can stack to form a superhelical spiral. Visual inspection of the extrapolated structure of 24 ankyrin-R repeats indicates the possibility of spring-like behaviour of the putative superhelix. Moreover, stacks of 17-29 ankyrin repeats in the cytoplasmic domains of transient receptor potential (TRP) channels have been identified as candidates for a spring that gates mechanoreceptors in hair cells as well as in Drosophila bristles. Here we report that tandem ankyrin repeats exhibit tertiary-structure-based elasticity and behave as a linear and fully reversible spring in single-molecule measurements by atomic force microscopy. We also observe an unexpected ability of unfolded repeats to generate force during refolding, and report the first direct measurement of the refolding force of a protein domain. Thus, we show that one of the most common amino-acid motifs has spring properties that could be important in mechanotransduction and in the design of nanodevices.

  14. Limitations on quantum key repeaters.

    PubMed

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  15. Magnetars as soft gamma repeaters

    NASA Astrophysics Data System (ADS)

    O'Meara, Karen

    1999-05-01

    The source of non-periodic, repeating, gamma-ray bursts located within our galaxy and near supernova remnants has been a mystery. A new theory by Christopher Thompson and Robert Duncan, postulating the existence of young neutron stars with intense magnetic fields (1E14 Gauss or more) offers an explanation. The intense magnetic fields of these "magnetars" suffice to create the phenomena detected from soft gamma-ray repeaters. The poles of a magnetar are hot enough to emit steady, low level x-ray emissions. Stresses on the star's crust due to the drifting of the magnetic field through the superfluid core create seismic activity and "starquakes," which release enormous bursts of energy. Data collected from recent soft gamma-ray repeater bursts appear to be strong evidence in support of this exciting new theory.

  16. Limitations on quantum key repeaters

    NASA Astrophysics Data System (ADS)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-01

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  17. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    NASA Astrophysics Data System (ADS)

    Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

    2014-02-01

    The Gd5Ge2Si2 alloy and the off-stoichiometric Ni50Mn35In15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd5Ge2Si2 and Ni50Mn35In15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  18. Do Twelfths Terminate or Repeat?

    ERIC Educational Resources Information Center

    Ambrose, Rebecca; Burnison, Erica

    2015-01-01

    When finding the decimal equivalent of a fraction with 12 in the denominator, will it terminate or repeat? This question came from a seventh grader in author Erica Burnison's class as the student was pondering a poster generated by one of her classmates. Not only was the question intriguing, but it also affirmed the belief in the power of…

  19. Mechanical Anisotropy of Ankyrin Repeats

    PubMed Central

    Lee, Whasil; Zeng, Xiancheng; Rotolo, Kristina; Yang, Ming; Schofield, Christopher J.; Bennett, Vann; Yang, Weitao; Marszalek, Piotr E.

    2012-01-01

    Red blood cells are frequently deformed and their cytoskeletal proteins such as spectrin and ankyrin-R are repeatedly subjected to mechanical forces. While the mechanics of spectrin was thoroughly investigated in vitro and in vivo, little is known about the mechanical behavior of ankyrin-R. In this study, we combine coarse-grained steered molecular dynamics simulations and atomic force spectroscopy to examine the mechanical response of ankyrin repeats (ARs) in a model synthetic AR protein NI6C, and in the D34 fragment of native ankyrin-R when these proteins are subjected to various stretching geometry conditions. Our steered molecular dynamics results, supported by AFM measurements, reveal an unusual mechanical anisotropy of ARs: their mechanical stability is greater when their unfolding is forced to propagate from the N-terminus toward the C-terminus (repeats unfold at ∼60 pN), as compared to the unfolding in the opposite direction (unfolding force ∼ 30 pN). This anisotropy is also reflected in the complex refolding behavior of ARs. The origin of this unfolding and refolding anisotropy is in the various numbers of native contacts that are broken and formed at the interfaces between neighboring repeats depending on the unfolding/refolding propagation directions. Finally, we discuss how these complex mechanical properties of ARs in D34 may affect its behavior in vivo. PMID:22404934

  20. Pentapeptide Repeat Proteins and Cyanobacteria

    SciTech Connect

    Buchko, Garry W.

    2009-10-16

    Cyanobacteria are unique in many ways and one unusual feature is the presence of a suite of proteins that contain at least one domain with a minimum of eight tandem repeated five-residues (Rfr) of the general consensus sequence A[N/D]LXX. The function of such pentapeptide repeat proteins (PRPs) are still unknown, however, their prevalence in cyanobacteria suggests that they may play some role in the unique biological activities of cyanobacteria. As part of an inter-disciplinary Membrane Biology Grand Challenge at the Environmental Molecular Sciences Laboratory (Pacific Northwest National Laboratory) and Washington University in St. Louis, the genome of Cyanothece 51142 was sequenced and its molecular biology studied with relation to circadian rhythms. The genome of Cyanothece encodes for 35 proteins that contain at least one PRP domain. These proteins range in size from 105 (Cce_3102) to 930 (Cce_2929) kDa with the PRP domains ranging in predicted size from 12 (Cce_1545) to 62 (cce_3979) tandem pentapeptide repeats. Transcriptomic studies with 29 out of the 35 genes showed that at least three of the PRPs in Cyanothece 51142 (cce_0029, cce_3083, and cce_3272) oscillated with repeated periods of light and dark, further supporting a biological function for PRPs. Using X-ray diffraction crystallography, the structure for two pentapeptide repeat proteins from Cyanothece 51142 were determined, cce_1272 (aka Rfr32) and cce_4529 (aka Rfr23). Analysis of their molecular structures suggests that all PRP may share the same structural motif, a novel type of right-handed quadrilateral β-helix, or Rfr-fold, reminiscent of a square tower with four distinct faces. Each pentapeptide repeat occupies one face of the Rfr-fold with four consecutive pentapeptide repeats completing a coil that, in turn, stack upon each other to form “protein skyscrapers”. Details of the structural features of the Rfr-fold are reviewed here together with a discussion for the possible role of end

  1. Dominant short repeated sequences in bacterial genomes.

    PubMed

    Avershina, Ekaterina; Rudi, Knut

    2015-03-01

    We use a novel multidimensional searching approach to present the first exhaustive search for all possible repeated sequences in 166 genomes selected to cover the bacterial domain. We found an overrepresentation of repeated sequences in all but one of the genomes. The most prevalent repeats by far were related to interspaced short palindromic repeats (CRISPRs)—conferring bacterial adaptive immunity. We identified a deep branching clade of thermophilic Firmicutes containing the highest number of CRISPR repeats. We also identified a high prevalence of tandem repeated heptamers. In addition, we identified GC-rich repeats that could potentially be involved in recombination events. Finally, we identified repeats in a 16322 amino acid mega protein (involved in biofilm formation) and inverted repeats flanking miniature transposable elements (MITEs). In conclusion, the exhaustive search for repeated sequences identified new elements and distribution of these, which has implications for understanding both the ecology and evolution of bacteria.

  2. Observations of Soft Gamma Repeaters

    NASA Technical Reports Server (NTRS)

    Kouveliotou, Chryssa

    2004-01-01

    Magnetars (Soft Gamma Repeaters and Anomalous X-ray Pulsars) are a subclass of neutron stars characterized by their recurrent X-ray bursts. While in an active (bursting) state (lasting anywhere between days and years), they are emit&ng hundreds of predominantly soft (kT=30 kev), short (0.1-100 ms long) events. Their quiescent source x-ray light ewes exhibit puhlions rotational period rate changes (spin-down) indicate that their magnetic fields are extremely high, of the order of 10^14- 10^l5 G. Such high B-field objects, dubbed "magnetars", had been predicted to exist in 1992, but the first concrete observational evidence were obtained in 1998 for two of these sources. I will discuss here the history of Soft Gamma Repeaters, and their spectral, timing and flux characteristics both in the persistent and their burst emission.

  3. A repeating fast radio burst

    NASA Astrophysics Data System (ADS)

    Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.

    2016-03-01

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  4. A repeating fast radio burst.

    PubMed

    Spitler, L G; Scholz, P; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-03-10

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  5. Comprehensive analysis of the transcriptional landscape of the human FMR1 gene reveals two new long noncoding RNAs differentially expressed in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome.

    PubMed

    Pastori, Chiara; Peschansky, Veronica J; Barbouth, Deborah; Mehta, Arpit; Silva, Jose P; Wahlestedt, Claes

    2014-01-01

    The majority of the human genome is transcribed but not translated, giving rise to noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs, >200 nt) that perform a wide range of functions in gene regulation. The Fragile X mental retardation 1 (FMR1) gene is a microsatellite locus that in the general population contains <55 CGG repeats in its 5'-untranslated region. Expansion of this repeat region to a size of 55-200 CGG repeats, known as premutation, is associated with Fragile X tremor and ataxia syndrome (FXTAS). Further expansion beyond 200 CGG repeats, or full mutation, leads to FMR1 gene silencing and results in Fragile X syndrome (FXS). Using a novel technology called "Deep-RACE", which combines rapid amplification of cDNA ends (RACE) with next generation sequencing, we systematically interrogated the FMR1 gene locus for the occurrence of novel lncRNAs. We discovered two transcripts, FMR5 and FMR6. FMR5 is a sense lncRNA transcribed upstream of the FMR1 promoter, whereas FMR6 is an antisense transcript overlapping the 3' region of FMR1. FMR5 was expressed in several human brain regions from unaffected individuals and from full and premutation patients. FMR6 was silenced in full mutation and, unexpectedly, in premutation carriers suggesting abnormal transcription and/or chromatin remodeling prior to transition to the full mutation. These lncRNAs may thus be useful as biomarkers, allowing for early detection and therapeutic intervention in FXS and FXTAS. Finally we show that FMR5 and FMR6 are expressed in peripheral blood leukocytes and propose future studies that correlate lncRNA expression with clinical outcomes.

  6. Altered neural activity in the 'when' pathway during temporal processing in fragile X premutation carriers.

    PubMed

    Kim, So-Yeon; Tassone, Flora; Simon, Tony J; Rivera, Susan M

    2014-03-15

    Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Large expansions of the CGG repeat (>200 repeats) consequently result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 of CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA. Recent studies have shown that infants with FXS exhibit severely reduced resolution of temporal attention, whereas spatial resolution of attention is not impaired. Following from these findings in the full mutation, the current study used fMRI to examine whether premutation carriers would exhibit atypical temporal processing at behavioral and/or neural levels. Using spatial and temporal working memory (SWM and TWM) tasks, separately tagging spatial and temporal processing, we demonstrated that neurotypical adults showed greater activation in the 'when pathway' (i.e., the right temporoparietal junction: TPJ) during TWM retrieval than SWM retrieval. However, premutation carriers failed to show this increased involvement of the right TPJ during retrieval of temporal information. Further, multiple regression analyses on right TPJ activation and FMR1 gene expression (i.e., CGG repeat size and FMR1 mRNA) suggests that elevated FMR1 mRNA level is a powerful predictor accounting for reduced right TPJ activation associated with temporal processing in premutation carriers. In conclusion, the current study provides the first evidence on altered neural correlates of temporal processing in adults with the premutation, explained by their FMR1 gene expression.

  7. FXTAS in an unmethylated mosaic male with fragile X syndrome from Chile.

    PubMed

    Santa María, L; Pugin, A; Alliende, M A; Aliaga, S; Curotto, B; Aravena, T; Tang, H-T; Mendoza-Morales, G; Hagerman, R; Tassone, F

    2014-10-01

    Carriers of an FMR1 premutation allele (55-200 CGG repeats) often develop the neurodegenerative disorders, fragile X-associated tremor/ataxia syndrome (FXTAS). Neurological signs of FXTAS, parkinsonism and rapid onset of cognitive decline have not been reported in individuals with an unmethylated full mutation (FM). Here, we report a Chilean family affected with FXS, inherited from a parent carrier of an FMR1 unmethylated full mosaic allele, who presented with a fast progressing FXTAS. This case suggests that the definition of FXTAS may need to be broadened to not only include those with a premutation but also those with an expanded allele in FM range with a lack of methylation leading to elevated FMR1-mRNA expression levels and subsequent RNA toxicity.

  8. Accumulate Repeat Accumulate Coded Modulation

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative coded modulation scheme called 'Accumulate Repeat Accumulate Coded Modulation' (ARA coded modulation). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes that are combined with high level modulation. Thus at the decoder belief propagation can be used for iterative decoding of ARA coded modulation on a graph, provided a demapper transforms the received in-phase and quadrature samples to reliability of the bits.

  9. Crowding by a repeating pattern

    PubMed Central

    Rosen, Sarah; Pelli, Denis G.

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target–flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker. PMID:26024457

  10. Crowding by a repeating pattern.

    PubMed

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  11. Evolution of Protein Domain Repeats in Metazoa

    PubMed Central

    Schüler, Andreas; Bornberg-Bauer, Erich

    2016-01-01

    Repeats are ubiquitous elements of proteins and they play important roles for cellular function and during evolution. Repeats are, however, also notoriously difficult to capture computationally and large scale studies so far had difficulties in linking genetic causes, structural properties and evolutionary trajectories of protein repeats. Here we apply recently developed methods for repeat detection and analysis to a large dataset comprising over hundred metazoan genomes. We find that repeats in larger protein families experience generally very few insertions or deletions (indels) of repeat units but there is also a significant fraction of noteworthy volatile outliers with very high indel rates. Analysis of structural data indicates that repeats with an open structure and independently folding units are more volatile and more likely to be intrinsically disordered. Such disordered repeats are also significantly enriched in sites with a high functional potential such as linear motifs. Furthermore, the most volatile repeats have a high sequence similarity between their units. Since many volatile repeats also show signs of recombination, we conclude they are often shaped by concerted evolution. Intriguingly, many of these conserved yet volatile repeats are involved in host-pathogen interactions where they might foster fast but subtle adaptation in biological arms races. Key Words: protein evolution, domain rearrangements, protein repeats, concerted evolution. PMID:27671125

  12. Repeated Reading. What Works Clearinghouse Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2014

    2014-01-01

    "Repeated reading" is an academic practice that aims to increase oral reading fluency. "Repeated reading" can be used with students who have developed initial word reading skills but demonstrate inadequate reading fluency for their grade level. During "repeated reading," a student sits in a quiet location with a…

  13. Altered structural brain connectome in young adult fragile X premutation carriers.

    PubMed

    Leow, Alex; Harvey, Danielle; Goodrich-Hunsaker, Naomi J; Gadelkarim, Johnson; Kumar, Anand; Zhan, Liang; Rivera, Susan M; Simon, Tony J

    2014-09-01

    Fragile X premutation carriers (fXPC) are characterized by 55-200 CGG trinucleotide repeats in the 5' untranslated region on the Xq27.3 site of the X chromosome. Clinically, they are associated with the fragile X-Associated Tremor/Ataxia Syndrome, a late-onset neurodegenerative disorder with diffuse white matter neuropathology. Here, we conducted first-ever graph theoretical network analyses in fXPCs using 30-direction diffusion-weighted magnetic resonance images acquired from 42 healthy controls aged 18-44 years (HC; 22 male and 20 female) and 46 fXPCs (16 male and 30 female). Globally, we found no differences between the fXPCs and HCs within each gender for all global graph theoretical measures. In male fXPCs, global efficiency was significantly negatively associated with the number of CGG repeats. For nodal measures, significant group differences were found between male fXPCs and male HCs in the right fusiform and the right ventral diencephalon (for nodal efficiency), and in the left hippocampus [for nodal clustering coefficient (CC)]. In female fXPCs, CC in the left superior parietal cortex correlated with counting performance in an enumeration task.

  14. X inactivation plays a major role in the gender bias in somatic expansion in a mouse model of the fragile X-related disorders: implications for the mechanism of repeat expansion.

    PubMed

    Adihe Lokanga, Rachel; Zhao, Xiao-Nan; Entezam, Ali; Usdin, Karen

    2014-09-15

    The Fragile X-related disorders are X-linked disorders resulting from the inheritance of FMR1 alleles with >54 CGG/CCG repeats in their 5' UTR. The repeats expand both somatically and on intergenerational transmission and increased repeat numbers are associated with increased risk of disease and increased risk of further expansion. The mechanism responsible for expansion is unknown. Here, we show in a knockin mouse model of these disorders that somatic expansion is much less common in females than in males. We show that this is due in large part to the fact that expansions occur only when the repeat is on the active X chromosome. However, even when this is taken into account, expansions in females are still less common than expected. This additional gender effect is not due to a protective effect of estrogen, a deleterious effect of testosterone or to differences in the expression of the Fmr1 gene or a variety of X-linked and autosomal DNA repair genes. However, our data do suggest that a higher level of expression of genes that protect against oxidative damage in females may contribute to their lower levels of expansion. Whatever the basis, our data suggest that the risk for somatic expansion may be lower in women than it is in men. This could help explain the reduced penetrance of some aspects of disease pathology in women. The fact that expansion only occurs when the Fmr1 allele is on the active X chromosome has important implications for the mechanism of repeat expansion.

  15. Two-dimensional quantum repeaters

    NASA Astrophysics Data System (ADS)

    Wallnöfer, J.; Zwerger, M.; Muschik, C.; Sangouard, N.; Dür, W.

    2016-11-01

    The endeavor to develop quantum networks gave rise to a rapidly developing field with far-reaching applications such as secure communication and the realization of distributed computing tasks. This ultimately calls for the creation of flexible multiuser structures that allow for quantum communication between arbitrary pairs of parties in the network and facilitate also multiuser applications. To address this challenge, we propose a two-dimensional quantum repeater architecture to establish long-distance entanglement shared between multiple communication partners in the presence of channel noise and imperfect local control operations. The scheme is based on the creation of self-similar multiqubit entanglement structures at growing scale, where variants of entanglement swapping and multiparty entanglement purification are combined to create high-fidelity entangled states. We show how such networks can be implemented using trapped ions in cavities.

  16. Linear Synchronous Motor Repeatability Tests

    SciTech Connect

    Ward, C.R.

    2002-10-18

    A cart system using linear synchronous motors was being considered for the Plutonium Immobilization Plant (PIP). One of the applications in the PIP was the movement of a stack of furnace trays, filled with the waste form (pucks) from a stacking/unstacking station to several bottom loaded furnaces. A system was ordered to perform this function in the PIP Ceramic Prototype Test Facility (CPTF). This system was installed and started up in SRTC prior to being installed in the CPTF. The PIP was suspended and then canceled after the linear synchronous motor system was started up. This system was used to determine repeatability of a linear synchronous motor cart system for the Modern Pit Facility.

  17. Repeat instability: mechanisms of dynamic mutations.

    PubMed

    Pearson, Christopher E; Nichol Edamura, Kerrie; Cleary, John D

    2005-10-01

    Disease-causing repeat instability is an important and unique form of mutation that is linked to more than 40 neurological, neurodegenerative and neuromuscular disorders. DNA repeat expansion mutations are dynamic and ongoing within tissues and across generations. The patterns of inherited and tissue-specific instability are determined by both gene-specific cis-elements and trans-acting DNA metabolic proteins. Repeat instability probably involves the formation of unusual DNA structures during DNA replication, repair and recombination. Experimental advances towards explaining the mechanisms of repeat instability have broadened our understanding of this mutational process. They have revealed surprising ways in which metabolic pathways can drive or protect from repeat instability.

  18. Unfolding a linker between helical repeats.

    PubMed

    Ortiz, Vanessa; Nielsen, Steven O; Klein, Michael L; Discher, Dennis E

    2005-06-10

    In many multi-repeat proteins, linkers between repeats have little secondary structure and place few constraints on folding or unfolding. However, the large family of spectrin-like proteins, including alpha-actinin, spectrin, and dystrophin, share three-helix bundle, spectrin repeats that appear in crystal structures to be linked by long helices. All of these proteins are regularly subjected to mechanical stress. Recent single molecule atomic force microscopy (AFM) experiments demonstrate not only forced unfolding but also simultaneous unfolding of tandem repeats at finite frequency, which suggests that the contiguous helix between spectrin repeats can propagate a cooperative helix-to-coil transition. Here, we address what happens atomistically to the linker under stress by steered molecular dynamics simulations of tandem spectrin repeats in explicit water. The results for alpha-actinin repeats reveal rate-dependent pathways, with one pathway showing that the linker between repeats unfolds, which may explain the single-repeat unfolding pathway observed in AFM experiments. A second pathway preserves the structural integrity of the linker, which explains the tandem-repeat unfolding event. Unfolding of the linker begins with a splay distortion of proximal loops away from hydrophobic contacts with the linker. This is followed by linker destabilization and unwinding with increased hydration of the backbone. The end result is an unfolded helix that mechanically decouples tandem repeats. Molecularly detailed insights obtained here aid in understanding the mechanical coupling of domain stability in spectrin family proteins.

  19. A Semiparametric Bayesian Model for Repeatedly Repeated Binary Outcomes

    PubMed Central

    Quintana, Fernando A.; Müller, Peter; Rosner, Gary L.; Relling, Mary V.

    2009-01-01

    Summary We discuss the analysis of data from single nucleotide polymorphism (SNP) arrays comparing tumor and normal tissues. The data consist of sequences of indicators for loss of heterozygosity (LOH) and involve three nested levels of repetition: chromosomes for a given patient, regions within chromosomes, and SNPs nested within regions. We propose to analyze these data using a semiparametric model for multi-level repeated binary data. At the top level of the hierarchy we assume a sampling model for the observed binary LOH sequences that arises from a partial exchangeability argument. This implies a mixture of Markov chains model. The mixture is defined with respect to the Markov transition probabilities. We assume a nonparametric prior for the random mixing measure. The resulting model takes the form of a semiparametric random effects model with the matrix of transition probabilities being the random effects. The model includes appropriate dependence assumptions for the two remaining levels of the hierarchy, i.e., for regions within chromosomes and for chromosomes within patient. We use the model to identify regions of increased LOH in a dataset coming from a study of treatment-related leukemia in children with an initial cancer diagnostic. The model successfully identifies the desired regions and performs well compared to other available alternatives. PMID:19746193

  20. Modeling Repeatedly Flaring δ Sunspots

    NASA Astrophysics Data System (ADS)

    Chatterjee, Piyali; Hansteen, Viggo; Carlsson, Mats

    2016-03-01

    Active regions (ARs) appearing on the surface of the Sun are classified into α , β , γ , and δ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the δ sunspots are known to be superactive and produce the most x-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin subphotospheric magnetic sheet breaks into multiple flux tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic δ sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  1. Modeling Repeatedly Flaring δ Sunspots.

    PubMed

    Chatterjee, Piyali; Hansteen, Viggo; Carlsson, Mats

    2016-03-11

    Active regions (ARs) appearing on the surface of the Sun are classified into α, β, γ, and δ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the δ sunspots are known to be superactive and produce the most x-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin subphotospheric magnetic sheet breaks into multiple flux tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic δ sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  2. Trinucleotide Repeats: A Structural Perspective

    PubMed Central

    Almeida, Bruno; Fernandes, Sara; Abreu, Isabel A.; Macedo-Ribeiro, Sandra

    2013-01-01

    Trinucleotide repeat (TNR) expansions are present in a wide range of genes involved in several neurological disorders, being directly involved in the molecular mechanisms underlying pathogenesis through modulation of gene expression and/or the function of the RNA or protein it encodes. Structural and functional information on the role of TNR sequences in RNA and protein is crucial to understand the effect of TNR expansions in neurodegeneration. Therefore, this review intends to provide to the reader a structural and functional view of TNR and encoded homopeptide expansions, with a particular emphasis on polyQ expansions and its role at inducing the self-assembly, aggregation and functional alterations of the carrier protein, which culminates in neuronal toxicity and cell death. Detail will be given to the Machado-Joseph Disease-causative and polyQ-containing protein, ataxin-3, providing clues for the impact of polyQ expansion and its flanking regions in the modulation of ataxin-3 molecular interactions, function, and aggregation. PMID:23801983

  3. TRDB—The Tandem Repeats Database

    PubMed Central

    Gelfand, Yevgeniy; Rodriguez, Alfredo; Benson, Gary

    2007-01-01

    Tandem repeats in DNA have been under intensive study for many years, first, as a consequence of their usefulness as genomic markers and DNA fingerprints and more recently as their role in human disease and regulatory processes has become apparent. The Tandem Repeats Database (TRDB) is a public repository of information on tandem repeats in genomic DNA. It contains a variety of tools for repeat analysis, including the Tandem Repeats Finder program, query and filtering capabilities, repeat clustering, polymorphism prediction, PCR primer selection, data visualization and data download in a variety of formats. In addition, TRDB serves as a centralized research workbench. It provides user storage space and permits collaborators to privately share their data and analysis. TRDB is available at . PMID:17175540

  4. Visual Scan Adaptation During Repeated Visual Search

    DTIC Science & Technology

    2010-01-01

    repeated distractor –target configurations both require environmental stability. For stable distractor – target configurations, Chun and Jiang (1998) have...demon- strated search time savings from repeating distractor –target configurations, and Song and Jiang (2005) demonstrated that as little as 25% of the...search environment (i.e., two distractor locations and the target location out of 12 total locations per trial) repeated from trial to trial resulted

  5. Short Tandem Repeat DNA Internet Database

    National Institute of Standards and Technology Data Gateway

    SRD 130 Short Tandem Repeat DNA Internet Database (Web, free access)   Short Tandem Repeat DNA Internet Database is intended to benefit research and application of short tandem repeat DNA markers for human identity testing. Facts and sequence information on each STR system, population data, commonly used multiplex STR systems, PCR primers and conditions, and a review of various technologies for analysis of STR alleles have been included.

  6. All repeats are not equal: a module-based approach to guide repeat protein design.

    PubMed

    Sawyer, Nicholas; Chen, Jieming; Regan, Lynne

    2013-05-27

    Repeat proteins composed of tandem arrays of a short structural motif often mediate protein-protein interactions. Past efforts to design repeat protein-based molecular recognition tools have focused on the creation of templates from the consensus of individual repeats, regardless of their natural context. Such an approach assumes that all repeats are essentially equivalent. In this study, we present the results of a "module-based" approach in which modules composed of tandem repeats are aligned to identify repeat-specific features. Using this approach to analyze tetratricopeptide repeat modules that contain three tandem repeats (3TPRs), we identify two classes of 3TPR modules with distinct structural signatures that are correlated with different sets of functional residues. Our analyses also reveal a high degree of correlation between positions across the entire ligand-binding surface, indicative of a coordinated, coevolving binding surface. Extension of our analyses to different repeat protein modules reveals more examples of repeat-specific features, especially in armadillo repeat modules. In summary, the module-based analyses that we present effectively capture key repeat-specific features that will be important to include in future repeat protein design templates.

  7. Reduced excitatory amino acid transporter 1 and metabotropic glutamate receptor 5 expression in the cerebellum of fragile X mental retardation gene 1 premutation carriers with fragile X-associated tremor/ataxia syndrome.

    PubMed

    Pretto, Dalyir I; Kumar, Madhur; Cao, Zhengyu; Cunningham, Christopher L; Durbin-Johnson, Blythe; Qi, Lihong; Berman, Robert; Noctor, Stephen C; Hagerman, Randi J; Pessah, Isaac N; Tassone, Flora

    2014-05-01

    A premutation (PM) expansion (55-200 CGG) in the fragile X mental retardation gene 1 causes elevated messenger RNA and reduced fragile X mental retardation gene 1 protein. Young PM carriers can develop characteristic physical features and mild cognitive disabilities. In addition, individuals with PM, particularly male carriers, are at high risk to develop fragile X-associated tremor/ataxia syndrome (FXTAS) with aging. Human postmortem FXTAS brains show extensive white matter disease in the cerebellum and the presence of intranuclear inclusions throughout the brain, although their etiologic significance is unknown. In the current work, expression levels of the metabotropic glutamate (Glu) receptor 5 and the Glu transporter excitatory amino acid transporter 1, examined by reverse transcription polymerase chain reaction and western blot analyses, were found to be reduced in the postmortem cerebellum of PM carriers with FXTAS compared with age matched controls, with higher CGG repeat number having greater reductions in both proteins. These data suggests a dysregulation of Glu signaling in PM carriers, which would likely contribute to the development and severity of FXTAS.

  8. A Comparison of DWI Repeaters and Non-repeaters Who Attended a Level I Rehabilitation Program.

    ERIC Educational Resources Information Center

    Landrum, James W.; Windham, Gerald O.

    1981-01-01

    Compares behavioral and demographic characteristics of drunk drivers with repeated arrests and drivers not having repeated arrests, after attending an alcohol education program. Previous public drunkeness and previous drunk driving arrests were strong predictors of repeat arrests and were judged useful in screening offenders for rehabilitation…

  9. Repeated Testing Produces Superior Transfer of Learning Relative to Repeated Studying

    ERIC Educational Resources Information Center

    Butler, Andrew C.

    2010-01-01

    The present research investigated whether test-enhanced learning can be used to promote transfer. More specifically, 4 experiments examined how repeated testing and repeated studying affected retention and transfer of facts and concepts. Subjects studied prose passages and then either repeatedly restudied or took tests on the material. One week…

  10. Length of FMR1 repeat alleles within the normal range does not substantially affect the risk of early menopause

    PubMed Central

    Ruth, Katherine S.; Bennett, Claire E.; Schoemaker, Minouk J.; Weedon, Michael N.; Swerdlow, Anthony J.; Murray, Anna

    2016-01-01

    estimate minor dilution of risk of early menopause from the likely inclusion of some women with menopause at over 45 years in the early menopause cases due to age-rounding bias in self-reports. WIDER IMPLICATIONS OF THE FINDINGS There is no robust evidence in this large study that variation within the normal range of FMR1 repeat alleles influences timing of menopause in the general population, which contradicts findings from some earlier, mainly smaller studies. The FMR1 CGG repeat polymorphism in the normal range is unlikely to contribute to genetic susceptibility to early menopause. STUDY FUNDING/COMPETING INTEREST(S) We thank Breast Cancer Now and The Institute of Cancer Research for funding the BGS. The Institute of Cancer Research acknowledges NHS funding to the NIHR Biomedical Research Centre. The study was funded by the Wellcome Trust (grant number 085943). There are no competing interests. TRIAL REGISTRATION NUMBER Not applicable. PMID:27614355

  11. Epigenetics and Triplet-Repeat Neurological Diseases.

    PubMed

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term "junk DNA" has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy's disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases.

  12. DNA Triplet Repeat Expansion and Mismatch Repair

    PubMed Central

    Iyer, Ravi R.; Pluciennik, Anna; Napierala, Marek; Wells, Robert D.

    2016-01-01

    DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway. PMID:25580529

  13. Cumulative Effect of Repeated Brief Cerebral Ischemia

    DTIC Science & Technology

    1993-05-31

    KL, Pohost GM and Conger KA, Correlating EEG and Lactate Kinetics During Repeated Brief Cerebral Ischemia, Proceedings of the American Heart Association 1993...Cornelating EEG and Lactate Kinetics During Repeated Brief Cerebral Ischemia, Proceedings of the American Heart Association 1993. 4) HP Hetherington...thes Bernhard Foundation. ass- 134 󈧑&.1 n5. 9# American Heart Association 026085 66th Scientific Sessions Abstract Form Medical Research Nursing

  14. Newly arisen DNA repeats in primate phylogeny.

    PubMed

    Ryan, S C; Dugaiczyk, A

    1989-12-01

    We discovered the presence of an Alu and an Xba repetitive DNA element within introns 4 and 7, respectively, of the human alpha-fetoprotein (AFP) gene; these elements are absent from the same gene in the gorilla. The Alu element is flanked by 12-base-pair direct repeats, AGGATGTTGTGG ... (Alu) ... AGGATGTTGTGG, which presumably arose by way of duplication of the intronic target site AGGATGTTGTGG at the time of the Alu insertion. In the gorilla, only a single copy of the unoccupied target site is present, which is identical to the terminal repeat flanking the human Alu element. There are two copies of an Xba repeat in the human AFP gene, apparently the only two in the genome. Xba1 and Xba2, located within introns 8 and 7, respectively, differ from each other at 3 of 303 positions. Xba1 is referred to as the old (ancestral) repeat because it lacks direct repeats. The new (derived) Xba2 is flanked by direct repeats, TTTCTTTTT ... (Xba) ... TTTCTTCTT, and is thought to have arisen as a result of transposition of Xba1. The ancestral Xba1 and a single copy of the Xba2 target site are present at orthologous positions in the gorilla, but the new Xba2 is absent. We conclude that the Alu and Xba DNA repeats emerged in the human genome at a time postdating the human-gorilla divergence and became established as genetic novelties in the human lineage. We submit that the chronology of divergence of primate lines of evolution can be correlated with the timing of insertion of new DNA repeats into the genomes of those primates.

  15. Repeat radiosurgery for cerebral arteriovenous malformations

    PubMed Central

    Stapleton, Christopher J.; Ding, Dale; Leed, Cheng-Chia; Loeffler, Jay S.

    2015-01-01

    We perform a systematic review of repeated radiosurgery for cerebral arteriovenous malformations (AVM) with an emphasis on lesion obliteration rates and complications. Radiosurgery is an accepted treatment modality for AVM located in eloquent cortex or deep brain structures. For residual or persistent lesions, repeated radiosurgery can be considered if sufficient time has passed to allow for a full appreciation of treatment effects, usually at least 3 years. A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. References for this review were identified by searches of MEDLINE, Web of Science and Google Scholar databases. A total of 14 studies comprising 733 patients met the review criteria and were included. For series that reported target dose at both first and repeat treatments, the weighted means were 19.42 Gy and 19.06 Gy, respectively. The mean and median obliteration rate for the repeat radiosurgery treatments were 61% (95% confidence interval 51.9–71.7%) and 61.5%, respectively. The median follow up following radiosurgery ranged from 19.5 to 80 months. Time to complete obliteration after the repeat treatment ranged from 21 to 40.8 months. The most common complications of repeated radiosurgery for AVM included hemorrhage (7.6%) and radiation-induced changes (7.4%). Repeat radiosurgery can be used to treat incompletely obliterated AVM with an obliteration rate of 61%. Complications are related to treatment effect latency (hemorrhage risk) as well as radiation-induced changes. Repeat radiosurgery can be performed at three years following the initial treatment, allowing for full realization of effects from the initial treatment prior to commencing therapy. PMID:25913746

  16. Digital repeat analysis; setup and operation.

    PubMed

    Nol, J; Isouard, G; Mirecki, J

    2006-06-01

    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  17. Dynamic combinatorial libraries of artificial repeat proteins.

    PubMed

    Eisenberg, Margarita; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2013-06-15

    Repeat proteins are found in almost all cellular systems, where they are involved in diverse molecular recognition processes. Recent studies have suggested that de novo designed repeat proteins may serve as universal binders, and might potentially be used as practical alternative to antibodies. We describe here a novel chemical methodology for producing small libraries of repeat proteins, and screening in parallel the ligand binding of library members. The first stage of this research involved the total synthesis of a consensus-based three-repeat tetratricopeptide (TPR) protein (~14 kDa), via sequential attachment of the respective peptides. Despite the effectiveness of the synthesis and ligation steps, this method was found to be too demanding for the production of proteins containing variable number of repeats. Additionally, the analysis of binding of the individual proteins was time consuming. Therefore, we designed and prepared novel dynamic combinatorial libraries (DCLs), and show that their equilibration can facilitate the formation of TPR proteins containing up to eight repeating units. Interestingly, equilibration of the library building blocks in the presence of the biologically relevant ligands, Hsp90 and Hsp70, induced their oligomerization into forming more of the proteins with large recognition surfaces. We suggest that this work presents a novel simple and rapid tool for the simultaneous screening of protein mixtures with variable binding surfaces, and for identifying new binders for ligands of interest.

  18. Proliferating cell nuclear antigen prevents trinucleotide repeat expansions by promoting repeat deletion and hairpin removal

    PubMed Central

    Beaver, Jill M.; Lai, Yanhao; Rolle, Shantell J.; Liu, Yuan

    2017-01-01

    DNA base lesions and base excision repair (BER) within trinucleotide repeat (TNR) tracts modulate repeat instability through the coordination among the key BER enzymes DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase I (LIG I). However, it remains unknown whether BER cofactors can also alter TNR stability. In this study, we discovered that proliferating cell nuclear antigen (PCNA), a cofactor of BER, promoted CAG repeat deletion and removal of a CAG repeat hairpin during BER in a duplex CAG repeat tract and CAG hairpin loop, respectively. We showed that PCNA stimulated LIG I activity on a nick across a small template loop during BER in a duplex (CAG)20 repeat tract promoting small repeat deletions. Surprisingly, we found that during BER in a hairpin loop, PCNA promoted reannealing of the upstream flap of a double-flap intermediate, thereby facilitating the formation of a downstream flap and stimulating FEN1 cleavage activity and hairpin removal. Our results indicate that PCNA plays a critical role in preventing CAG repeat expansions by modulating the structures of dynamic DNA via cooperation with BER enzymes. We provide the first evidence that PCNA prevents CAG repeat expansions during BER by promoting CAG repeat deletion and removal of a TNR hairpin. PMID:27793507

  19. Automated genotyping of dinucleotide repeat markers

    SciTech Connect

    Perlin, M.W.; Hoffman, E.P. |

    1994-09-01

    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  20. Role of memory errors in quantum repeaters

    NASA Astrophysics Data System (ADS)

    Hartmann, L.; Kraus, B.; Briegel, H.-J.; Dür, W.

    2007-03-01

    We investigate the influence of memory errors in the quantum repeater scheme for long-range quantum communication. We show that the communication distance is limited in standard operation mode due to memory errors resulting from unavoidable waiting times for classical signals. We show how to overcome these limitations by (i) improving local memory and (ii) introducing two operational modes of the quantum repeater. In both operational modes, the repeater is run blindly, i.e., without waiting for classical signals to arrive. In the first scheme, entanglement purification protocols based on one-way classical communication are used allowing to communicate over arbitrary distances. However, the error thresholds for noise in local control operations are very stringent. The second scheme makes use of entanglement purification protocols with two-way classical communication and inherits the favorable error thresholds of the repeater run in standard mode. One can increase the possible communication distance by an order of magnitude with reasonable overhead in physical resources. We outline the architecture of a quantum repeater that can possibly ensure intercontinental quantum communication.

  1. Spectrin repeat proteins in the nucleus.

    PubMed

    Young, Kevin G; Kothary, Rashmi

    2005-02-01

    Spectrin repeat sequences are among the more common repeat elements identified in proteins, typically occurring in large structural proteins. Examples of spectrin repeat-containing proteins include dystrophin, alpha-actinin and spectrin itself--all proteins with well-demonstrated roles of establishing and maintaining cell structure. Over the past decade, it has become clear that, although these proteins display a cytoplasmic and plasma membrane distribution, several are also found both at the nuclear envelope, and within the intranuclear space. In this review, we provide an overview of recent work regarding various spectrin repeat-containing structural proteins in the nucleus. As well, we hypothesize about the regulation of their nuclear localization and possible nuclear functions based on domain architecture, known interacting proteins and evolutionary relationships. Given their large size, and their potential for interacting with multiple proteins and with chromatin, spectrin repeat-containing proteins represent strong candidates for important organizational proteins within the nucleus. Supplementary material for this article can be found on the BioEssays website (http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html).

  2. Rate analysis for a hybrid quantum repeater

    SciTech Connect

    Bernardes, Nadja K.; Loock, Peter van

    2011-01-15

    We present a detailed rate analysis for a hybrid quantum repeater assuming perfect memories and using optimal probabilistic entanglement generation and deterministic swapping routines. The hybrid quantum repeater protocol is based on atomic qubit-entanglement distribution through optical coherent-state communication. An exact, analytical formula for the rates of entanglement generation in quantum repeaters is derived, including a study on the impacts of entanglement purification and multiplexing strategies. More specifically, we consider scenarios with as little purification as possible and we show that for sufficiently low local losses, such purifications are still more powerful than multiplexing. In a possible experimental scenario, our hybrid system can create near-maximally entangled (F=0.98) pairs over a distance of 1280 km at rates of the order of 100 Hz.

  3. Hematuria home screening: repeat testing results.

    PubMed

    Messing, E M; Young, T B; Hunt, V B; Newton, M A; Bram, L L; Vaillancourt, A; Hisgen, W J; Greenberg, E B; Kuglitsch, M E; Wegenke, J D

    1995-07-01

    To determine at what interval screening should be repeated to detect bladder cancer before it becomes muscle invasive 856 men who had 14 negative daily home tests for hematuria with a chemical reagent strip 9 months previously performed repeat tests. Of these men 50 (5.8%) had at least 1 positive test during the second 14-day screening period and 38 were evaluated, 15 of whom (39.5%) had significant urological pathological conditions, including 8 with malignancies. Bladder cancer was noted in 7 men, with no tumor invading the muscularis propria. The finding of 7 bladder cancers in 856 men (0.82%) who had a negative test 9 months previously indicates that bladder cancer has a brief preclinical duration and that testing must be repeated at least annually for screening to detect bladder cancer consistently before invasion occurs.

  4. Some characteristics of repeated sickness absence

    PubMed Central

    Ferguson, David

    1972-01-01

    Ferguson, D. (1972).Brit. J. industr. Med.,29, 420-431. Some characteristics of repeated sickness absence. Several studies have shown that frequency of absence attributed to sickness is not distributed randomly but tends to follow the negative binomial distribution, and this has been taken to support the concept of `proneness' to such absence. Thus, the distribution of sickness absence resembles that of minor injury at work demonstrated over 50 years ago. Because the investigation of proneness to absence does not appear to have been reported by others in Australia, the opportunity was taken, during a wider study of health among telegraphists in a large communications undertaking, to analyse some characteristics of repeated sickness absence. The records of medically certified and uncertified sickness absence of all 769 telegraphists continuously employed in all State capitals over a two-and-a-half-year period were compared with those of 411 clerks and 415 mechanics and, in Sydney, 380 mail sorters and 80 of their supervisors. All telegraphists in Sydney, Melbourne, and Brisbane, and all mail sorters in Sydney, who were available and willing were later medically examined. From their absence pattern repeaters (employees who had had eight or more certified absences in two and a half years) were separated into three types based on a presumptive origin in chance, recurrent disease and symptomatic non-specific disorder. The observed distribution of individual frequency of certified absence over the full two-and-a-half-year period of study followed that expected from the univariate negative binomial, using maximum likelihood estimators, rather than the poisson distribution, in three of the four occupational groups in Sydney. Limited correlational and bivariate analysis supported the interpretation of proneness ascribed to the univariate fit. In the two groups studied, frequency of uncertified absence could not be fitted by the negative binomial, although the numbers of

  5. Do gamma-ray burst sources repeat?

    NASA Technical Reports Server (NTRS)

    Meegan, Charles A.; Hartmann, Dieter H.; Brainerd, J. J.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey; Kouveliotou, Chryssa; Fishman, Gerald; Blumenthal, George; Brock, Martin

    1995-01-01

    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb, 1993; Wang and Lingenfelter, 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al., 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the observed bursts cannot be excluded.

  6. Formation of the Arabidopsis pentatricopeptide repeat family.

    PubMed

    Rivals, Eric; Bruyère, Clémence; Toffano-Nioche, Claire; Lecharny, Alain

    2006-07-01

    In Arabidopsis (Arabidopsis thaliana) the 466 pentatricopeptide repeat (PPR) proteins are putative RNA-binding proteins with essential roles in organelles. Roughly half of the PPR proteins form the plant combinatorial and modular protein (PCMP) subfamily, which is land-plant specific. PCMPs exhibit a large and variable tandem repeat of a standard pattern of three PPR variant motifs. The association or not of this repeat with three non-PPR motifs at their C terminus defines four distinct classes of PCMPs. The highly structured arrangement of these motifs and the similar repartition of these arrangements in the four classes suggest precise relationships between motif organization and substrate specificity. This study is an attempt to reconstruct an evolutionary scenario of the PCMP family. We developed an innovative approach based on comparisons of the proteins at two levels: namely the succession of motifs along the protein and the amino acid sequence of the motifs. It enabled us to infer evolutionary relationships between proteins as well as between the inter- and intraprotein repeats. First, we observed a polarized elongation of the repeat from the C terminus toward the N-terminal region, suggesting local recombinations of motifs. Second, the most N-terminal PPR triple motif proved to evolve under different constraints than the remaining repeat. Altogether, the evidence indicates different evolution for the PPR region and the C-terminal one in PCMPs, which points to distinct functions for these regions. Moreover, local sequence homogeneity observed across PCMP classes may be due to interclass shuffling of motifs, or to deletions/insertions of non-PPR motifs at the C terminus.

  7. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    SciTech Connect

    Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  8. Safety of Repeated Yttrium-90 Radioembolization

    SciTech Connect

    Lam, Marnix G. E. H.; Louie, John D.; Iagaru, Andrei H.; Goris, Michael L.; Sze, Daniel Y.

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  9. Therapeutics development for triplet repeat expansion diseases.

    PubMed

    Di Prospero, Nicholas A; Fischbeck, Kenneth H

    2005-10-01

    The underlying genetic mutations for many inherited neurodegenerative disorders have been identified in recent years. One frequent type of mutation is trinucleotide repeat expansion. Depending on the location of the repeat expansion, the mutation might result in a loss of function of the disease gene, a toxic gain of function or both. Disease gene identification has led to the development of model systems for investigating disease mechanisms and evaluating treatments. Examination of experimental findings reveals similarities in disease mechanisms as well as possibilities for treatment.

  10. Effect of Repeated Evaluation and Repeated Exposure on Acceptability Ratings of Sentences

    ERIC Educational Resources Information Center

    Zervakis, Jennifer; Mazuka, Reiko

    2013-01-01

    This study investigated the effect of repeated evaluation and repeated exposure on grammatical acceptability ratings for both acceptable and unacceptable sentence types. In Experiment 1, subjects in the Experimental group rated multiple examples of two ungrammatical sentence types (ungrammatical binding and double object with dative-only verb),…

  11. Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects

    PubMed Central

    Reichen, Christian; Madhurantakam, Chaithanya; Hansen, Simon; Grütter, Markus G.; Plückthun, Andreas; Mittl, Peer R. E.

    2016-01-01

    The armadillo repeat serves as a scaffold for the development of modular peptide-recognition modules. In order to develop such a system, three crystal structures of designed armadillo-repeat proteins with third-generation N-caps (YIII-type), four or five internal repeats (M-type) and second-generation C-caps (AII-type) were determined at 1.8 Å (His-YIIIM4AII), 2.0 Å (His-YIIIM5AII) and 1.95 Å (YIIIM5AII) resolution and compared with those of variants with third-generation C-caps. All constructs are full consensus designs in which the internal repeats have exactly the same sequence, and hence identical conformations of the internal repeats are expected. The N-cap and internal repeats M1 to M3 are indeed extremely similar, but the comparison reveals structural differences in internal repeats M4 and M5 and the C-cap. These differences are caused by long-range effects of the C-cap, contacting molecules in the crystal, and the intrinsic design of the repeat. Unfortunately, the rigid-body movement of the C-terminal part impairs the regular arrangement of internal repeats that forms the putative peptide-binding site. The second-generation C-cap improves the packing of buried residues and thereby the stability of the protein. These considerations are useful for future improvements of an armadillo-repeat-based peptide-recognition system. PMID:26894544

  12. Triggering of repeating earthquakes in central California

    USGS Publications Warehouse

    Wu, Chunquan; Gomberg, Joan; Ben-Naim, Eli; Johnson, Paul

    2014-01-01

    Dynamic stresses carried by transient seismic waves have been found capable of triggering earthquakes instantly in various tectonic settings. Delayed triggering may be even more common, but the mechanisms are not well understood. Catalogs of repeating earthquakes, earthquakes that recur repeatedly at the same location, provide ideal data sets to test the effects of transient dynamic perturbations on the timing of earthquake occurrence. Here we employ a catalog of 165 families containing ~2500 total repeating earthquakes to test whether dynamic perturbations from local, regional, and teleseismic earthquakes change recurrence intervals. The distance to the earthquake generating the perturbing waves is a proxy for the relative potential contributions of static and dynamic deformations, because static deformations decay more rapidly with distance. Clear changes followed the nearby 2004 Mw6 Parkfield earthquake, so we study only repeaters prior to its origin time. We apply a Monte Carlo approach to compare the observed number of shortened recurrence intervals following dynamic perturbations with the distribution of this number estimated for randomized perturbation times. We examine the comparison for a series of dynamic stress peak amplitude and distance thresholds. The results suggest a weak correlation between dynamic perturbations in excess of ~20 kPa and shortened recurrence intervals, for both nearby and remote perturbations.

  13. Chlorinated hydrocarbons in women with repeated miscarriages.

    PubMed Central

    Gerhard, I; Daniel, V; Link, S; Monga, B; Runnebaum, B

    1998-01-01

    This study was conducted to investigate a possible etiological role of chlorinated hydrocarbons in the pathogenesis of repeated miscarriages. The blood levels of chlorinated hydrocarbons [CHCs: pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, the dichlorodiphenyltrichloroethane (DDT) group, polychlorinated biphenyls] were determined in 89 women with repeated miscarriages, who were referred to the University Hospital of Obstetrics and Gynecology of Heidelberg for investigations between 1989 and 1993, and compared to a previously investigated reference population. In more than 20% of the women, at least one of the CHC levels exceeded the reference range. CHC levels did not differ significantly between women with primary or secondary and early or late miscarriages; neither did they differ between women with hormonal or immunological disorders as causes of repeated miscarriages or women with idiopathic repeated miscarriages. No significant associations were detected between CHC levels and further conceptions or the outcome of further pregnancies. As significant associations were found between increasing CHC blood concentrations and immunological and hormonal changes, CHCs may have an impact on the pregnancy course in certain cases. PMID:9755145

  14. Is Retrieval Mediated after Repeated Testing?

    ERIC Educational Resources Information Center

    Kole, James A.; Healy, Alice F.

    2013-01-01

    In 2 main experiments, the mediated priming effect was used to determine whether retrieval continues to be mediated after repeated testing. In each experiment, participants used the keyword method to learn French vocabulary, then completed a modified lexical decision task in which they first translated a French word, and then made a lexical…

  15. Repeater For A Digital-Communication Bus

    NASA Technical Reports Server (NTRS)

    Torres-Guzman, Esteban; Olson, Stephen; Heaps, Tim

    1993-01-01

    Digital repeater circuit designed to extend range of communication on MIL-STD-1553 bus beyond original maximum allowable length of 300 ft. Circuit provides two-way communication, one way at time, and conforms to specifications of MIL-STD-1553. Crosstalk and instability eliminated.

  16. Rectourethral fistula after repeat transrectal prostate biopsy.

    PubMed

    Loran, Oleg B; Veliev, Evgeny I; Sokolov, Egor A; Dadashev, Elmar O; Guspanov, Renat I

    2013-09-01

    Transrectal prostate biopsy is considered a relatively safe procedure, with a quite small number of complications. We report a patient with a rectourethral fistula after a repeat transrectal prostate biopsy. To our knowledge, this is the first incident in the published literature.

  17. Repeated Random Sampling in Year 5

    ERIC Educational Resources Information Center

    Watson, Jane M.; English, Lyn D.

    2016-01-01

    As an extension to an activity introducing Year 5 students to the practice of statistics, the software "TinkerPlots" made it possible to collect repeated random samples from a finite population to informally explore students' capacity to begin reasoning with a distribution of sample statistics. This article provides background for the…

  18. [Preventive maintenance of repeated ischemic insults].

    PubMed

    Gavrilenko, A V; Kuklin, A V; Kravchenko, A A; Agafonov, I N

    2008-01-01

    In the review we offer analysis of the effectiveness of carotid endarterectomy in treatment of post-functional apoplexy or stroke patients. Published results of the researches specify possible efficiency of carotid endarterectomy in preventive maintenance against repeated apoplectic attack or strokes. Yet the criteria of usage and execution of the carotid endarterectomy are still to be discussed.

  19. Epigenetics and Triplet-Repeat Neurological Diseases

    PubMed Central

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term “junk DNA” has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy’s disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases. PMID:26733936

  20. Testing Multiple Outcomes in Repeated Measures Designs

    ERIC Educational Resources Information Center

    Lix, Lisa M.; Sajobi, Tolulope

    2010-01-01

    This study investigates procedures for controlling the familywise error rate (FWR) when testing hypotheses about multiple, correlated outcome variables in repeated measures (RM) designs. A content analysis of RM research articles published in 4 psychology journals revealed that 3 quarters of studies tested hypotheses about 2 or more outcome…

  1. Y Se Repite = And It Repeats Itself

    ERIC Educational Resources Information Center

    Katzew, Adriana

    2010-01-01

    In this article, the author discusses Y Se Repite [And It Repeats Itself], a project she conceptualized due to the growing number of Latino/a Mexican migrant workers in dairy farms in the state of Vermont. In 2006, approximately 2,000 Latinos/as--most of them undocumented Mexican migrant workers--worked throughout the state's dairy farms, yet…

  2. Longer-baseline telescopes using quantum repeaters.

    PubMed

    Gottesman, Daniel; Jennewein, Thomas; Croke, Sarah

    2012-08-17

    We present an approach to building interferometric telescopes using ideas of quantum information. Current optical interferometers have limited baseline lengths, and thus limited resolution, because of noise and loss of signal due to the transmission of photons between the telescopes. The technology of quantum repeaters has the potential to eliminate this limit, allowing in principle interferometers with arbitrarily long baselines.

  3. The Effect of Repeaters on Equating

    ERIC Educational Resources Information Center

    Kim, HeeKyoung; Kolen, Michael J.

    2010-01-01

    Test equating might be affected by including in the equating analyses examinees who have taken the test previously. This study evaluated the effect of including such repeaters on Medical College Admission Test (MCAT) equating using a population invariance approach. Three-parameter logistic (3-PL) item response theory (IRT) true score and…

  4. Repeated sprint training in normobaric hypoxia.

    PubMed

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-12-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4 ± 1.5 years, 1.83 ± 0.07 m, 88.1 ± 8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10 × 6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO₂) or normoxia (21% FiO₂). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10 × 6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33 ± 12%) than the normoxic group (14 ± 10%, p<0.05). During the 10 × 6 s RS test there was a tendency for greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9 ± 9%, normoxic (-0.3 ± 8.8%, p=0.06) and reductions in cerebral deoxygenation (% changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS training sessions in hypoxia resulted in twofold greater improvements in capacity to perform repeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block.

  5. Repeated sprint training in normobaric hypoxia

    PubMed Central

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-01-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4±1.5 years, 1.83±0.07 m, 88.1±8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10×6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO2) or normoxia (21% FiO2). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10×6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33±12%) than the normoxic group (14±10%, p<0.05). During the 10×6 s RS test there was a tendency for greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9±9%, normoxic (−0.3±8.8%, p=0.06) and reductions in cerebral deoxygenation (% changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS training sessions in hypoxia resulted in twofold greater improvements in capacity to perform repeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block. PMID:24282212

  6. RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures

    PubMed Central

    Paladin, Lisanna; Hirsh, Layla; Piovesan, Damiano; Andrade-Navarro, Miguel A.; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2017-01-01

    RepeatsDB 2.0 (URL: http://repeatsdb.bio.unipd.it/) is an update of the database of annotated tandem repeat protein structures. Repeat proteins are a widespread class of non-globular proteins carrying heterogeneous functions involved in several diseases. Here we provide a new version of RepeatsDB with an improved classification schema including high quality annotations for ∼5400 protein structures. RepeatsDB 2.0 features information on start and end positions for the repeat regions and units for all entries. The extensive growth of repeat unit characterization was possible by applying the novel ReUPred annotation method over the entire Protein Data Bank, with data quality is guaranteed by an extensive manual validation for >60% of the entries. The updated web interface includes a new search engine for complex queries and a fully re-designed entry page for a better overview of structural data. It is now possible to compare unit positions, together with secondary structure, fold information and Pfam domains. Moreover, a new classification level has been introduced on top of the existing scheme as an independent layer for sequence similarity relationships at 40%, 60% and 90% identity. PMID:27899671

  7. Vectorette PCR isolation of microsatellite repeat sequences using anchored dinucleotide repeat primers.

    PubMed Central

    Lench, N J; Norris, A; Bailey, A; Booth, A; Markham, A F

    1996-01-01

    We have developed a vectorette PCR approach to provide an improved method for isolation of microsatellite repeats. The modified procedure relies on PCR amplification using a vectorette-specific primer in combination with one of a panel of anchored dinucleotide repeat primers. The target DNA to be screened for microsatellite sequences can be from YAC, P1, cosmid, bacteriophage or plasmid clones. We have used this technique to isolate novel, polymorphic microsatellite repeats from clones containing the amelogenin gene (AMGX) located on human chromosome Xp22.3. PMID:8668553

  8. Fragile X-associated tremor/ataxia syndrome.

    PubMed

    Hagerman, Paul J; Hagerman, Randi J

    2015-03-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some but not all carriers of small, noncoding CGG-repeat expansions (55-200 repeats; premutation) within the fragile X gene (FMR1). Principal features of FXTAS include intention tremor, cerebellar ataxia, Parkinsonism, memory and executive function deficits, autonomic dysfunction, brain atrophy with white matter disease, and cognitive decline. Although FXTAS was originally considered to be confined to the premutation range, rare individuals with a gray zone (45-54 repeats) or an unmethylated full mutation (>200 repeats) allele have now been described, the constant feature of the disorder remaining the requirement for FMR1 expression, in contradistinction to the gene silencing mechanism of fragile X syndrome. Although transcriptional activity is required for FXTAS pathogenesis, the specific trigger(s) for FXTAS pathogenesis remains elusive, highlighting the need for more research in this area. This need is underscored by recent neuroimaging findings of changes in the central nervous system that consistently appear well before the onset of clinical symptoms, thus creating an opportunity to delay or prevent the appearance of FXTAS.

  9. Stability of dental waxes following repeated heatings.

    PubMed

    Kotsiomiti, E; McCabe, J F

    1995-02-01

    The flow and strength properties of dental waxes were examined following excessive and repeated heatings of the materials. For one product, the flow at 40 +/- 0.5 degrees C was reduced by 25.3% following heating above 200 degrees C. A decrease of the elastic modulus at 20 +/- 1 degree C by approximately 66% was observed in some cases after the heating temperature had been increased to 300 degrees C. Property variations were related to compositional changes, which were investigated by infrared spectoscopy and thermal analysis. Exposure of dental waxes to temperatures higher than 200 degrees C, particularly if it is repeated, may affect the composition and properties, resulting in inferior materials.

  10. Overcoming fixation with repeated memory suppression.

    PubMed

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  11. Mutagenic inverted repeat assisted genome engineering (MIRAGE).

    PubMed

    Nair, Nikhil U; Zhao, Huimin

    2009-01-01

    Here we describe a one-step method to create precise modifications in the genome of Saccharomyces cerevisiae as a tool for synthetic biology, metabolic engineering, systems biology and genetic studies. Through homologous recombination, a mutagenesis cassette containing an inverted repeat of selection marker(s) is integrated into the genome. Due to its inherent instability in genomic DNA, the inverted repeat catalyzes spontaneous self-excision, resulting in precise genome modification. Since this excision occurs at very high frequencies, selection for the integration event can be followed immediately by counterselection, without the need for growth in permissive conditions. This is the first time a truly one-step method has been described for genome modification in any organism.

  12. Accumulate-Repeat-Accumulate-Accumulate Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Samuel; Thorpe, Jeremy

    2007-01-01

    Accumulate-repeat-accumulate-accumulate (ARAA) codes have been proposed, inspired by the recently proposed accumulate-repeat-accumulate (ARA) codes. These are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. ARAA codes can be regarded as serial turbolike codes or as a subclass of low-density parity-check (LDPC) codes, and, like ARA codes they have projected graph or protograph representations; these characteristics make it possible to design high-speed iterative decoders that utilize belief-propagation algorithms. The objective in proposing ARAA codes as a subclass of ARA codes was to enhance the error-floor performance of ARA codes while maintaining simple encoding structures and low maximum variable node degree.

  13. Repeat-PPM Super-Symbol Synchronization

    NASA Astrophysics Data System (ADS)

    Connelly, J.

    2016-11-01

    To attain a wider range of data rates in pulse position modulation (PPM) schemes with constrained pulse durations, the sender can repeat a PPM symbol multiple times, forming a super-symbol. In addition to the slot and symbol synchronization typically required for PPM, the receiver must also properly align the noisy super-symbols. We present a low-complexity approximation of the maximum-likelihood method for performing super-symbol synchronization without use of synchronization sequences. We provide simulation results demonstrating performance advantage when PPM symbols are spread by a pseudo-noise sequence, as opposed to simply repeating. Additionally, the results suggest that this super-symbol synchronization technique requires signal levels below those required for reliable communication. This validates that the PPM spreading approach proposed to CCSDS can work properly as part of the overall scheme.

  14. Repeated interactions in open quantum systems

    SciTech Connect

    Bruneau, Laurent; Joye, Alain; Merkli, Marco

    2014-07-15

    Analyzing the dynamics of open quantum systems has a long history in mathematics and physics. Depending on the system at hand, basic physical phenomena that one would like to explain are, for example, convergence to equilibrium, the dynamics of quantum coherences (decoherence) and quantum correlations (entanglement), or the emergence of heat and particle fluxes in non-equilibrium situations. From the mathematical physics perspective, one of the main challenges is to derive the irreversible dynamics of the open system, starting from a unitary dynamics of the system and its environment. The repeated interactions systems considered in these notes are models of non-equilibrium quantum statistical mechanics. They are relevant in quantum optics, and more generally, serve as a relatively well treatable approximation of a more difficult quantum dynamics. In particular, the repeated interaction models allow to determine the large time (stationary) asymptotics of quantum systems out of equilibrium.

  15. Nucleosome repeat lengths and columnar chromatin structure.

    PubMed

    Trifonov, Edward N

    2016-06-01

    Thorough quantitative study of nucleosome repeat length (NRL) distributions, conducted in 1992 by J. Widom, resulted in a striking observation that the linker lengths between the nucleosomes are quantized. Comparison of the NRL average values with the MNase cut distances predicted from the hypothetical columnar structure of chromatin (this work) shows a close correspondence between the two. This strongly suggests that the NRL distribution, actually, reflects the dominant role of columnar chromatin structure common for all eukaryotes.

  16. Identical repeated backbone of the human genome

    PubMed Central

    2010-01-01

    Background Identical sequences with a minimal length of about 300 base pairs (bp) have been involved in the generation of various meiotic/mitotic genomic rearrangements through non-allelic homologous recombination (NAHR) events. Genomic disorders and structural variation, together with gene remodelling processes have been associated with many of these rearrangements. Based on these observations, we identified and integrated all the 100% identical repeats of at least 300 bp in the NCBI version 36.2 human genome reference assembly into non-overlapping regions, thus defining the Identical Repeated Backbone (IRB) of the reference human genome. Results The IRB sequences are distributed all over the genome in 66,600 regions, which correspond to ~2% of the total NCBI human genome reference assembly. Important structural and functional elements such as common repeats, segmental duplications, and genes are contained in the IRB. About 80% of the IRB bp overlap with known copy-number variants (CNVs). By analyzing the genes embedded in the IRB, we were able to detect some identical genes not previously included in the Ensembl release 50 annotation of human genes. In addition, we found evidence of IRB gene copy-number polymorphisms in raw sequence reads of two diploid sequenced genomes. Conclusions In general, the IRB offers new insight into the complex organization of the identical repeated sequences of the human genome. It provides an accurate map of potential NAHR sites which could be used in targeting the study of novel CNVs, predicting DNA copy-number variation in newly sequenced genomes, and improve genome annotation. PMID:20096123

  17. Repeatability of Response to Asthma Medications

    PubMed Central

    Wu, Ann; Tantisira, Kelan; Li, Lingling; Schuemann, Brooke; Weiss, Scott

    2010-01-01

    Background Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients, however, no formal studies have demonstrated this. Objective To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, forced expiratory volume in 1 second (FEV1), and provocative concentration of methacholine producing a 20% decline in FEV1 (PC20). Methods The Childhood Asthma Management Program (CAMP) was a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over four years in CAMP using mixed effects regression models. We adjusted for the covariates: age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. Results The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV1 was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. Conclusion The within treatment group repeatability of FEV1 and PC20 are high; thus these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma. PMID:19064281

  18. 2D Metals by Repeated Size Reduction.

    PubMed

    Liu, Hanwen; Tang, Hao; Fang, Minghao; Si, Wenjie; Zhang, Qinghua; Huang, Zhaohui; Gu, Lin; Pan, Wei; Yao, Jie; Nan, Cewen; Wu, Hui

    2016-10-01

    A general and convenient strategy for manufacturing freestanding metal nanolayers is developed on large scale. By the simple process of repeatedly folding and calendering stacked metal sheets followed by chemical etching, free-standing 2D metal (e.g., Ag, Au, Fe, Cu, and Ni) nanosheets are obtained with thicknesses as small as 1 nm and with sizes of the order of several micrometers.

  19. Automatic-repeat-request error control schemes

    NASA Technical Reports Server (NTRS)

    Lin, S.; Costello, D. J., Jr.; Miller, M. J.

    1983-01-01

    Error detection incorporated with automatic-repeat-request (ARQ) is widely used for error control in data communication systems. This method of error control is simple and provides high system reliability. If a properly chosen code is used for error detection, virtually error-free data transmission can be attained. Various types of ARQ and hybrid ARQ schemes, and error detection using linear block codes are surveyed.

  20. Genomic Repeat Abundances Contain Phylogenetic Signal

    PubMed Central

    Dodsworth, Steven; Chase, Mark W.; Kelly, Laura J.; Leitch, Ilia J.; Macas, Jiří; Novák, Petr; Piednoël, Mathieu; Weiss-Schneeweiss, Hanna; Leitch, Andrew R.

    2015-01-01

    A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution. PMID:25261464

  1. Landauer's Principle in Repeated Interaction Systems

    NASA Astrophysics Data System (ADS)

    Hanson, Eric P.; Joye, Alain; Pautrat, Yan; Raquépas, Renaud

    2017-01-01

    We study Landauer's Principle for Repeated Interaction Systems (RIS) consisting of a reference quantum system S in contact with a structured environment E made of a chain of independent quantum probes; S interacts with each probe, for a fixed duration, in sequence. We first adapt Landauer's lower bound, which relates the energy variation of the environment E to a decrease of entropy of the system S during the evolution, to the peculiar discrete time dynamics of RIS. Then we consider RIS with a structured environment E displaying small variations of order {T^{-1}} between the successive probes encountered by S, after {n ˜eq T} interactions, in keeping with adiabatic scaling. We establish a discrete time non-unitary adiabatic theorem to approximate the reduced dynamics of S in this regime, in order to tackle the adiabatic limit of Landauer's bound. We find that saturation of Landauer's bound is related to a detailed balance condition on the repeated interaction system, reflecting the non-equilibrium nature of the repeated interaction system dynamics. This is to be contrasted with the generic saturation of Landauer's bound known to hold for continuous time evolution of an open quantum system interacting with a single thermal reservoir in the adiabatic regime.

  2. Agreement and repeatability of an infrared thermometer.

    PubMed

    Kelechi, Teresa J; Good, Angela; Mueller, Martina

    2011-01-01

    Recently, manufacturers have devised thermometers for home use by patients, such as the TempTouch Infrared Thermometer (TTIR; Diabetica Solutions, San Antonio, TX), which is designed with a long handle that can be used for self-monitoring localized skin temperature of the feet and legs. This study assessed the level of agreement and repeatability of the TTIR compared to a thermistor-type thermometer (TT; PeriFlux, 5020 Temperature Unit, Perimed, Stockholm, Sweden), the reference standard. In 17 healthy subjects, localized skin temperature was measured 8 cm above the right medial malleolus at baseline (Time 1), after a 10-minute rest period (Time 2), and after 10 minutes of cold provocation (Time 3) with a cryotherapy gel wrap placed around the lower legs using the TTIR and TT for temperature measurement. Scatter plots and correlation coefficients showed strong positive relationships between the two measurement methods at all three time points (Time 1: r = 0.95; Time 2: r = 0.97; and, Time 3: r = 0.87). Results showed a reasonable level of agreement between the two methods at Times 1 and 2 but not after cold provocation. Agreement between the methods appears to be better than repeatability within each method. Results for repeatability from both the TT and TTIR were very similar suggesting that there was a systematic bias with increasing temperatures between Time 1 and Time 2.

  3. Repeated-sprint ability: where are we?

    PubMed

    Dawson, Brian

    2012-09-01

    Repeated-sprint ability (RSA) is now well accepted as an important fitness component in team-sport performance. It is broadly described as the ability to perform repeated short (~3-4 s, 20-30 m) sprints with only brief (~10-30 s) recovery between bouts. Over the past 25 y a plethora of RSA tests have been trialed and reported in the literature. These range from a single set of ~6-10 short sprints, departing every 20-30 s, to team-sport game simulations involving repeating cycles of walk-jog-stride-sprint movements over 45-90 min. Such a wide range of RSA tests has not assisted the synthesis of research findings in this area, and questions remain regarding the optimal methods of training to best improve RSA. In addition, how RSA test scores relate to player "work rate," match performance, or both requires further investigation to improve the application of RSA testing and training to elite team-sport athletes.

  4. Accumulate-Repeat-Accumulate-Accumulate-Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Sam; Thorpe, Jeremy

    2004-01-01

    Inspired by recently proposed Accumulate-Repeat-Accumulate (ARA) codes [15], in this paper we propose a channel coding scheme called Accumulate-Repeat-Accumulate-Accumulate (ARAA) codes. These codes can be seen as serial turbo-like codes or as a subclass of Low Density Parity Check (LDPC) codes, and they have a projected graph or protograph representation; this allows for a high-speed iterative decoder implementation using belief propagation. An ARAA code can be viewed as a precoded Repeat-and-Accumulate (RA) code with puncturing in concatenation with another accumulator, where simply an accumulator is chosen as the precoder; thus ARAA codes have a very fast encoder structure. Using density evolution on their associated protographs, we find examples of rate-lJ2 ARAA codes with maximum variable node degree 4 for which a minimum bit-SNR as low as 0.21 dB from the channel capacity limit can be achieved as the block size goes to infinity. Such a low threshold cannot be achieved by RA or Irregular RA (IRA) or unstructured irregular LDPC codes with the same constraint on the maximum variable node degree. Furthermore by puncturing the accumulators we can construct families of higher rate ARAA codes with thresholds that stay close to their respective channel capacity thresholds uniformly. Iterative decoding simulation results show comparable performance with the best-known LDPC codes but with very low error floor even at moderate block sizes.

  5. Orthologous repeats and mammalian phylogenetic inference

    PubMed Central

    Bashir, Ali; Ye, Chun; Price, Alkes L.; Bafna, Vineet

    2005-01-01

    Determining phylogenetic relationships between species is a difficult problem, and many phylogenetic relationships remain unresolved, even among eutherian mammals. Repetitive elements provide excellent markers for phylogenetic analysis, because their mode of evolution is predominantly homoplasy-free and unidirectional. Historically, phylogenetic studies using repetitive elements have relied on biological methods such as PCR analysis, and computational inference is limited to a few isolated repeats. Here, we present a novel computational method for inferring phylogenetic relationships from partial sequence data using orthologous repeats. We apply our method to reconstructing the phylogeny of 28 mammals, using more than 1000 orthologous repeats obtained from sequence data available from the NISC Comparative Sequencing Program. The resulting phylogeny has robust bootstrap numbers, and broadly matches results from previous studies which were obtained using entirely different data and methods. In addition, we shed light on some of the debatable aspects of the phylogeny. With rapid expansion of available partial sequence data, computational analysis of repetitive elements holds great promise for the future of phylogenetic inference. PMID:15998912

  6. Repeat Stereotactic Radiosurgery for Acoustic Neuromas

    SciTech Connect

    Kano, Hideyuki; Kondziolka, Douglas; Niranjan, Ajay M.Ch.; Flannery, Thomas J.; Flickinger, John C.; Lunsford, L. Dade

    2010-02-01

    Purpose: To evaluate the outcome of repeat stereotactic radiosurgery (SRS) for acoustic neuromas, we assessed tumor control, clinical outcomes, and the risk of adverse radiation effects in patients whose tumors progressed after initial management. Methods and Materials: During a 21-year experience at our center, 1,352 patients underwent SRS as management for their acoustic neuromas. We retrospectively identified 6 patients who underwent SRS twice for the same tumor. The median patient age was 47 years (range, 35-71 years). All patients had imaging evidence of tumor progression despite initial SRS. One patient also had incomplete surgical resection after initial SRS. All patients were deaf at the time of the second SRS. The median radiosurgery target volume at the time of the initial SRS was 0.5 cc and was 2.1 cc at the time of the second SRS. The median margin dose at the time of the initial SRS was 13 Gy and was 11 Gy at the time of the second SRS. The median interval between initial SRS and repeat SRS was 63 months (range, 25-169 months). Results: At a median follow-up of 29 months after the second SRS (range, 13-71 months), tumor control or regression was achieved in all 6 patients. No patient developed symptomatic adverse radiation effects or new neurological symptoms after the second SRS. Conclusions: With this limited experience, we found that repeat SRS for a persistently enlarging acoustic neuroma can be performed safely and effectively.

  7. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    NASA Astrophysics Data System (ADS)

    Bagchi, Manjari

    2017-04-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  8. Repeatability of a running heat tolerance test.

    PubMed

    Mee, Jessica A; Doust, Jo; Maxwell, Neil S

    2015-01-01

    At present there is no standardised heat tolerance test (HTT) procedure adopting a running mode of exercise. Current HTTs may misdiagnose a runner's susceptibility to a hyperthermic state due to differences in exercise intensity. The current study aimed to establish the repeatability of a practical running test to evaluate individual's ability to tolerate exercise heat stress. Sixteen (8M, 8F) participants performed the running HTT (RHTT) (30 min, 9 km h(-1), 2% elevation) on two separate occasions in a hot environment (40 °C and 40% relative humidity). There were no differences in peak rectal temperature (RHTT1: 38.82 ± 0.47 °C, RHTT2: 38.86 ± 0.49 °C, Intra-class correlation coefficient (ICC)=0.93, typical error of measure (TEM) = 0.13 °C), peak skin temperature (RHTT1: 38.12 ± 0.45, RHTT2: 38.11 ± 0.45 °C, ICC = 0.79, TEM = 0.30 °C), peak heart rate (RHTT1: 182 ± 15 beats min(-1), RHTT2: 183 ± 15 beats min(-1), ICC = 0.99, TEM = 2 beats min(-1)), nor sweat rate (1721 ± 675 g h(-1), 1716 ± 745 g h(-1), ICC = 0.95, TEM = 162 g h(-1)) between RHTT1 and RHTT2 (p>0.05). Results demonstrate good agreement, strong correlations and small differences between repeated trials, and the TEM values suggest low within-participant variability. The RHTT was effective in differentiating between individuals physiological responses; supporting a heat tolerance continuum. The findings suggest the RHTT is a repeatable measure of physiological strain in the heat and may be used to assess the effectiveness of acute and chronic heat alleviating procedures.

  9. Are all repeats created equal? Understanding DNA repeats at an individual level.

    PubMed

    Yang, Jinpu; Li, Fei

    2017-02-01

    Repetitive DNA sequences, comprising up to 50 % of the genome in all eukaryotes, play important roles in a wide range of cellular functions, such as transcriptional regulation, genome stability, and cellular differentiation. However, due to technical difficulties in differentiating their sequences, DNA repeats remain one of the most mysterious parts of eukaryotic genomes. Key questions, such as how repetitive entities behave at individual level and how the internal architecture of these repeats is organized, are still poorly understood. Recent advances from our group reveal unexpected position-dependent variation within tandem DNA repeats in fission yeast. Despite sharing identical DNA sequences, the peri-centromeric repeats are organized into diverse epigenetic states and chromatin structures. We demonstrate that this position-dependent variation requires key heterochromatin factors and condensin. Our works further suggest that the peri-centromeric repeats are organized into distinct higher order structures that ensure a proper positioning of CENP-A, the centromere-specific histone H3 variant, to centromeres. These most recent developments offer insights into the mechanisms underlying the position effect within tandem DNA arrays, and have broad implications in the field of epigenetics and chromatin biology.

  10. Repeats identification using improved suffix trees.

    PubMed

    Huo, Hongwei; Wang, Xiaowu; Stojkovic, Vojislav

    2009-01-01

    The suffix tree data structure plays an important role in the efficient implementations of some querying algorithms. This paper presents the fast Rep(eats)Seeker algorithm for repeats identification based on the improvements of suffix tree construction. The leaf nodes and the branch nodes are numbered in different ways during the construction of a suffix tree and extra information is added to the branch nodes. The experimental results show that improvements reduce the running time of the RepSeeker algorithm without losing the accuracy. The experimental results coincide with the theoretical expectations.

  11. Distillation by repeated measurements: Continuous spectrum case

    SciTech Connect

    Bellomo, Bruno; Compagno, Giuseppe; Nakazato, Hiromichi; Yuasa, Kazuya

    2010-12-15

    Repeated measurements on one part of a bipartite system strongly affect the other part that is not measured, the dynamics of which is regulated by an effective contracted evolution operator. When the spectrum of this operator is discrete, the nonmeasured system is driven into a pure state, irrespective of the initial state, provided that the spectrum satisfies certain conditions. We show here that, even in the case of continuous spectrum, an effective distillation can occur under rather general conditions. We confirm it by applying our formalism to a simple model.

  12. Platelet peripheral benzodiazepine receptors in repeated stress

    SciTech Connect

    Dar, D.E.; Bidder, M.; Gavish, M. ); Weizman, A.; Karp, L.; Tyano, S. ); Grinshpoon, A.; Bleich, A.

    1991-01-01

    ({sup 3}H)PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.

  13. Platelet peripheral benzodiazepine receptors in repeated stress.

    PubMed

    Dar, D E; Weizman, A; Karp, L; Grinshpoon, A; Bidder, M; Kotler, M; Tyano, S; Bleich, A; Gavish, M

    1991-01-01

    [3H]PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced (26%; P less than 0.05) density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.

  14. Repeatable assessment protocol for electromagnetic trackers

    NASA Astrophysics Data System (ADS)

    Haidegger, Tamas; Sirokai, Beáta; Fenyvesi, Gábor; Kovács, Levente; Benyó, Balázs; Benyó, Zoltán

    2012-02-01

    In the past decades, many new trends appeared in interventional medicine. One of the most groundbreaking ones is Image-Guided Surgery (IGS). The main benefit of IGS procedures is the reduction of the patient's pain and collateral damage through improved accuracy and targeting. Electromagnetic Tracking (EMT) has been introduced to medical applications as an effective tool for navigation. However, magnetic fields can be severely distorted by ferromagnetic materials and electronic equipment, which is a major barrier towards their wider application. The focus of the study is to determine and compensate the inherent errors of the different types of EMTs, in order to improve their accuracy. Our aim is to develop a standardized, simple and repeatable assessment protocol; to determine tracking errors with sub-millimeter accuracy, hence increasing the measurement precision and reliability. For initial experiments, the NDI Aurora and the Ascension medSAFE systems were used in a standard laboratory environment. We aim to advance to the state-of-the art by describing and disseminating an easily reproducible calibration method, publishing the CAD files of the accuracy phantom and the source of the evaluation data. This should allow the wider spread of the technique, and eventually lead to the repeatable and comparable assessment of EMT systems.

  15. Distributed parameter modeling of repeated truss structures

    NASA Technical Reports Server (NTRS)

    Wang, Han-Ching

    1994-01-01

    A new approach to find homogeneous models for beam-like repeated flexible structures is proposed which conceptually involves two steps. The first step involves the approximation of 3-D non-homogeneous model by a 1-D periodic beam model. The structure is modeled as a 3-D non-homogeneous continuum. The displacement field is approximated by Taylor series expansion. Then, the cross sectional mass and stiffness matrices are obtained by energy equivalence using their additive properties. Due to the repeated nature of the flexible bodies, the mass, and stiffness matrices are also periodic. This procedure is systematic and requires less dynamics detail. The first step involves the homogenization from a 1-D periodic beam model to a 1-D homogeneous beam model. The periodic beam model is homogenized into an equivalent homogeneous beam model using the additive property of compliance along the generic axis. The major departure from previous approaches in literature is using compliance instead of stiffness in homogenization. An obvious justification is that the stiffness is additive at each cross section but not along the generic axis. The homogenized model preserves many properties of the original periodic model.

  16. Analysis of a random repeated impact process

    NASA Astrophysics Data System (ADS)

    Wood, L. A.; Byrne, K. P.

    1981-10-01

    A simple random repeated impact process similar to the classical random walk process is analyzed. The process, which consists of a ball bouncing on a randomly vibrating surface, is analogous to loss-of-contact situations which can occur in linkages and vibrating tools. It also has relevance to rolling contact where the rolling element may separate from the surface and sustain repeated impacts. A coefficient of restitution is used to describe impact, and some important assumptions limit the analysis to values of this coefficient greater than 0°8. The Markov nature of the process is demonstrated by its one-step "memory". It may be regarded as a discrete Markov process "imbedded" in continuous time. A difference equation governing the process is developed and analyzed for the case where the vibrating surface has a Gaussian distribution of velocities. With the one-step transition probability density function a linear weighting function is used to account for the weighting effect of the ball's velocity on the distribution of table velocities at impact. The resulting integral equation is solved iteratively to yield the probability density function of ball velocities after impact. This information may then be used to predict the magnitudes of the impacts and the time between them.

  17. Repeated proton beam therapy for hepatocellular carcinoma

    SciTech Connect

    Hashimoto, Takayuki |. E-mail: hashimoto@pmrc.tsukuba.ac.jp; Tokuuye, Koichi |; Fukumitsu, Nobuyoshi |; Igaki, Hiroshi |; Hata, Masaharu |; Kagei, Kenji |; Sugahara, Shinji; Ohara, Kiyoshi; Matsuzaki, Yasushi; Akine, Yasuyuki |

    2006-05-01

    Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A.

  18. Airborne Radar Interferometric Repeat-Pass Processing

    NASA Technical Reports Server (NTRS)

    Hensley, Scott; Michel, Thierry R.; Jones, Cathleen E.; Muellerschoen, Ronald J.; Chapman, Bruce D.; Fore, Alexander; Simard, Marc; Zebker, Howard A.

    2011-01-01

    Earth science research often requires crustal deformation measurements at a variety of time scales, from seconds to decades. Although satellites have been used for repeat-track interferometric (RTI) synthetic-aperture-radar (SAR) mapping for close to 20 years, RTI is much more difficult to implement from an airborne platform owing to the irregular trajectory of the aircraft compared with microwave imaging radar wavelengths. Two basic requirements for robust airborne repeat-pass radar interferometry include the ability to fly the platform to a desired trajectory within a narrow tube and the ability to have the radar beam pointed in a desired direction to a fraction of a beam width. Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) is equipped with a precision auto pilot developed by NASA Dryden that allows the platform, a Gulfstream III, to nominally fly within a 5 m diameter tube and with an electronically scanned antenna to position the radar beam to a fraction of a beam width based on INU (inertial navigation unit) attitude angle measurements.

  19. Chromosome-specific DNA Repeat Probes

    SciTech Connect

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  20. Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).

    PubMed

    O'Keefe, Joan A; Robertson-Dick, Erin; Dunn, Emily J; Li, Yan; Deng, Youping; Fiutko, Amber N; Berry-Kravis, Elizabeth; Hall, Deborah A

    2015-12-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a "premutation" size 55-200 CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Core motor features include cerebellar gait ataxia and kinetic tremor, resulting in progressive mobility disability. There are no published studies characterizing balance deficits in FMR1 premutation carriers with and without FXTAS using a battery of quantitative measures to test the sensory integration underlying postural control, automatic postural reflexes, and dynamic postural stability limits. Computerized dynamic posturography (CDP) and two performance-based balance measures were administered in 44 premutation carriers, 21 with FXTAS and 23 without FXTAS, and 42 healthy controls to compare balance and functional mobility between these groups. Relationships between FMR1 molecular variables, age, and sex and CDP scores were explored. FXTAS subjects demonstrated significantly lower scores on the sensory organization test (with greatest reductions in the vestibular control of balance), longer response latencies to balance perturbations, and reduced stability limits compared to controls. Premutation carriers without FXTAS also demonstrated significantly delayed response latencies and disrupted sensory weighting for balance control. Advancing age, male sex, increased CGG repeat size, and reduced X activation of the normal allele in premutation carrier women predicted balance dysfunction. These postural control deficits in carriers with and without FXTAS implicate dysfunctional cerebellar neural networks and may provide valuable outcome markers for tailored rehabilitative interventions. Our findings suggest that CDP may provide sensitive measures for early detection of postural control impairments in at-risk carriers and better characterize balance dysfunction and progression in FXTAS.

  1. High functioning male with fragile X syndrome and fragile X-associated tremor/ataxia syndrome.

    PubMed

    Basuta, Kirin; Schneider, Andrea; Gane, Louise; Polussa, Jonathan; Woodruff, Bryan; Pretto, Dalyir; Hagerman, Randi; Tassone, Flora

    2015-09-01

    Fragile X syndrome (FXS) affects individuals with more than 200 CGG repeats (full mutation) in the fragile X mental retardation 1 (FMR1) gene. Those born with FXS experience cognitive and social impairments, developmental delays, and some features of autism spectrum disorders. Carriers of a premutation (55-200 CGG repeats) are generally not severely affected early in life; however, are at high risk of developing the late onset neurodegenerative disorder, Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), or Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and may have other medical conditions such as developmental delay, autism spectrum disorders, hypertension, anxiety, and immune-mediated disorders. Here we present a case of a 58-year-old man with a borderline IQ, average memory skills, and executive function deficits. He met criteria for multiple psychiatric diagnoses and presented with tremor and ataxia, meeting criteria for FXTAS. Molecular testing unveiled a completely unmethylated FMR1 full mutation in peripheral blood mononucleated cells with elevated FMR1 mRNA and premutation alleles of different sizes in two other tissues (primary fibroblasts and sperm), indicating the presence of allele instability based on both inter- and intra-tissue mosaicism. The observation of FXTAS in this case of a full mutation mosaic man suggests that the pathogenic mechanism underlying this disorder is not observed exclusively in premutation carriers as it was originally thought. The concomitant presence of features of FXS and late onset neurological deterioration with probable FXTAS likely result from a combined molecular pathology of elevated FMR1 mRNA levels, a molecular hallmark of FXTAS and low FMRP expression that leads to FXS.

  2. Analysis of LRRK2 accessory repeat domains: prediction of repeat length, number and sites of Parkinson's disease mutations.

    PubMed

    Mills, Ryan D; Mulhern, Terrence D; Cheng, Heung-Chin; Culvenor, Janetta G

    2012-10-01

    Various investigators have identified the major domain organization of LRRK2 (leucine-rich repeat kinase 2), which includes a GTPase ROC (Ras of complex proteins) domain followed by a COR (C-terminal of ROC) domain and a protein kinase domain. In addition, there are four domains composed of structural repeat motifs likely to be involved in regulation and localization of this complex protein. In the present paper, we report our bioinformatic analyses of the human LRRK2 amino acid sequence to predict the repeat size, number and likely boundaries for the armadillo repeat, ankyrin repeat, the leucine-rich repeat and WD40 repeat regions of LRRK2. Homology modelling using known protein structures with similar domains was used to predict structures, exposed residues and location of mutations for these repeat regions. We predict that the armadillo repeats, ankyrin repeats and leucine-rich repeats together form an extended N-terminal flexible 'solenoid'-like structure composed of tandem repeat modules likely to be important in anchoring to the membrane and cytoskeletal structures as well as binding to other protein ligands. Near the C-terminus of LRRK2, the WD40 repeat region is predicted to form a closed propeller structure that is important for protein complex formation.

  3. Erroneous Memories Arising from Repeated Attempts to Remember

    ERIC Educational Resources Information Center

    Henkel, Linda A.

    2004-01-01

    The impact of repeated and prolonged attempts at remembering on false memory rates was assessed in three experiments. Participants saw and imagined pictures and then made repeated recall attempts before taking a source memory test. Although the number of items recalled increased with repeated tests, the net gains were associated with more source…

  4. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2.

    PubMed

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten; Skovby, Flemming; Hjermind, Lena E; Nielsen, Jørgen E; Nielsen, Troels Tolstrup

    2013-06-01

    The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective genes leading to pathogenic expansions of polyglutamine stretches in the encoded proteins. In general, unstable CAG repeats have an uninterrupted CAG repeat, whereas stable CAG repeats are either short or interrupted by CAA codons, which - like CAG codons - code for glutamine. Here we report on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency of paternal germ-line repeat sequence instability of the expanded SCA2 locus.

  5. Who Repeats Algebra, and How Does Initial Performance Relate to Improvement When the Course Is Repeated?

    ERIC Educational Resources Information Center

    Fong, Anthony; Jaquet, Karina; Finkelstein, Neal

    2016-01-01

    The information provided in this report shows how students perform when they repeat algebra I and how the level of improvement varies depending on initial course performance and the academic measure (course grades or CST scores). This information can help inform decisions and policies regarding whether and under what circumstances students should…

  6. Tandemly repeated exons encode 81-base repeats in multiple, developmentally regulated Schistosoma mansoni transcripts.

    PubMed Central

    Davis, R E; Davis, A H; Carroll, S M; Rajkovic, A; Rottman, F M

    1988-01-01

    The adult Schistosoma mansoni cDNA clone 10-3 encodes an antigen that is recognized by sera from infected humans. We characterized multiple developmentally regulated transcripts homologous to the 10-3 cDNA and portions of the complex genomic loci encoding those transcripts. Transcripts of approximately 950, 870, and 780 nucleotides were expressed in adults, whereas only the 780-nucleotide transcript was observed in the larval stage. These transcripts were highly similar, containing variable numbers of identical direct tandem repeats of 81 bases. Although the sequence of the repeating elements and sequences 3' to them were identical in all the transcripts, sequences 5' of the repeating elements exhibited variations, including a 27-base insertion, alternative start sites for transcription, and alternate 5' exon usage. These transcripts appeared to be derived in part by the developmentally controlled alternative splicing of small exons and the use of alternative transcription initiation sites from the one or two complex loci of at least 40 kilobase pairs. Each 81-base repeat in the transcripts was encoded by three dispersed 27-base-pair exons. These 27-base-pair exons were contained within highly conserved, reiterated 3-kilobase-pair genomic tandem arrays. Images PMID:3211127

  7. Repeat Testing Effects on Credentialing Exams: Are Repeaters Misinformed or Uninformed?

    ERIC Educational Resources Information Center

    Feinberg, Richard A.; Raymond, Mark R.; Haist, Steven A.

    2015-01-01

    To mitigate security concerns and unfair score gains, credentialing programs routinely administer new test material to examinees retesting after an initial failing attempt. Counterintuitively, a small but growing body of recent research suggests that repeating the identical form does not create an unfair advantage. This study builds upon and…

  8. Quantum repeaters using continuous-variable teleportation

    NASA Astrophysics Data System (ADS)

    Dias, Josephine; Ralph, T. C.

    2017-02-01

    Quantum optical states are fragile and can become corrupted when passed through a lossy communication channel. Unlike for classical signals, optical amplifiers cannot be used to recover quantum signals. Quantum repeaters have been proposed as a way of reducing errors and hence increasing the range of quantum communications. Current protocols target specific discrete encodings, for example quantum bits encoded on the polarization of single photons. We introduce a more general approach that can reduce the effect of loss on any quantum optical encoding, including those based on continuous variables such as the field amplitudes. We show that in principle the protocol incurs a resource cost that scales polynomially with distance. We analyze the simplest implementation and find that while its range is limited it can still achieve useful improvements in the distance over which quantum entanglement of field amplitudes can be distributed.

  9. Simple sequence repeats in bryophyte mitochondrial genomes.

    PubMed

    Zhao, Chao-Xian; Zhu, Rui-Liang; Liu, Yang

    2016-01-01

    Simple sequence repeats (SSRs) are thought to be common in plant mitochondrial (mt) genomes, but have yet to be fully described for bryophytes. We screened the mt genomes of two liverworts (Marchantia polymorpha and Pleurozia purpurea), two mosses (Physcomitrella patens and Anomodon rugelii) and two hornworts (Phaeoceros laevis and Nothoceros aenigmaticus), and detected 475 SSRs. Some SSRs are found conserved during the evolution, among which except one exists in both liverworts and mosses, all others are shared only by the two liverworts, mosses or hornworts. SSRs are known as DNA tracts having high mutation rates; however, according to our observations, they still can evolve slowly. The conservativeness of these SSRs suggests that they are under strong selection and could play critical roles in maintaining the gene functions.

  10. Design principles for efficient, repeated jumpgliding.

    PubMed

    Desbiens, Alexis Lussier; Pope, Morgan T; Christensen, David L; Hawkes, Elliot W; Cutkosky, Mark R

    2014-06-01

    Combined jumping and gliding locomotion, or 'jumpgliding', can be an efficient way for small robots or animals to travel over cluttered terrain. This paper presents functional requirements and models for a simple jumpglider which formalize the benefits and limitations of using aerodynamic surfaces to augment jumping ability. Analysis of the model gives insight into design choices and control strategies for higher performance and to accommodate special conditions such as a slippery launching surface. The model informs the design of a robotic platform that can perform repeated jumps using a carbon fiber spring and a pivoting wing. Experiments with two different versions of the platform agree with predictions from the model and demonstrate a significantly greater range, and lower cost-of-transport, than a comparable ballistic jumper.

  11. Detection of repeating and "anti-repeating" earthquakes in the Bucaramanga Nest

    NASA Astrophysics Data System (ADS)

    Barrett, S. A.; Prieto, G.; Beroza, G. C.

    2011-12-01

    The Bucaramanga Nest, beneath northern Colombia represents the densest concentration of intermediate-depth earthquakes in the world. The roughly 11 km3 volume produces approximately 15 events per day, yielding an active catalog of seismicity well separated from surrounding seismic activity. We correlate template-event waveforms from known earthquakes to continuous records from the Colombian National (RSNC) seismic network. Typical repeating events are identified as well as the more curious "anti-repeat" events for which seismograms show reversed polarity and nearly perfect anti-correlation. These events are of particular interest as they are not known for shallow, crustal earthquake populations. By compiling a more complete catalog of earthquakes, and by developing precise relative locations, we seek to understand the temporal and size variations of these recurring events in the Bucaramanga Nest.

  12. Evolution of subterminal satellite (StSat) repeats in hominids.

    PubMed

    Koga, Akihiko; Notohara, Morihiro; Hirai, Hirohisa

    2011-02-01

    Subterminal satellite (StSat) repeats, consisting of 32-bp-long AT-rich units (GATATTTCCATGTT(T/C)ATACAGATAGCGGTGTA), were first found in chimpanzee and gorilla (African great apes) as one of the major components of heterochromatic regions located proximal to telomeres of chromosomes. StSat repeats have not been found in orangutan (Asian great ape) or human. This patchy distribution among species suggested that the StSat repeats were present in the common ancestor of African great apes and subsequently lost in the lineage leading to human. An alternative explanation is that the StSat repeats in chimpanzee and gorilla have different origins and the repeats did not occur in human. The purpose of the present study was quantitative evaluation of the above alternative possibilities by analyzing the nucleotide variation contained in the repeats. We collected large numbers of sequences of repeat units from genome sequence databases of chimpanzee and gorilla, and also bonobo (an African great ape phylogenetically closer to chimpanzee). We then compared the base composition of the repeat units among the 3 species, and found statistically significant similarities in the base composition. These results support the view that the StSat repeats had already formed multiple arrays in the common ancestor of African great apes. It is thus suggested that humans lost StSat repeats which had once grown to multiple arrays.

  13. Comparison of simple sequence repeats in 19 Archaea.

    PubMed

    Trivedi, S

    2006-12-05

    All organisms that have been studied until now have been found to have differential distribution of simple sequence repeats (SSRs), with more SSRs in intergenic than in coding sequences. SSR distribution was investigated in Archaea genomes where complete chromosome sequences of 19 Archaea were analyzed with the program SPUTNIK to find di- to penta-nucleotide repeats. The number of repeats was determined for the complete chromosome sequences and for the coding and non-coding sequences. Different from what has been found for other groups of organisms, there is an abundance of SSRs in coding regions of the genome of some Archaea. Dinucleotide repeats were rare and CG repeats were found in only two Archaea. In general, trinucleotide repeats are the most abundant SSR motifs; however, pentanucleotide repeats are abundant in some Archaea. Some of the tetranucleotide and pentanucleotide repeat motifs are organism specific. In general, repeats are short and CG-rich repeats are present in Archaea having a CG-rich genome. Among the 19 Archaea, SSR density was not correlated with genome size or with optimum growth temperature. Pentanucleotide density had an inverse correlation with the CG content of the genome.

  14. ATXN2 trinucleotide repeat length correlates with risk of ALS.

    PubMed

    Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar

    2017-03-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R(2) = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.

  15. PRIGSA: protein repeat identification by graph spectral analysis.

    PubMed

    Chakrabarty, Broto; Parekh, Nita

    2014-12-01

    Repetition of a structural motif within protein is associated with a wide range of structural and functional roles. In most cases the repeating units are well conserved at the structural level while at the sequence level, they are mostly undetectable suggesting the need for structure-based methods. Since most known methods require a training dataset, de novo approach is desirable. Here, we propose an efficient graph-based approach for detecting structural repeats in proteins. In a protein structure represented as a graph, interactions between inter- and intra-repeat units are well captured by the eigen spectra of adjacency matrix of the graph. These conserved interactions give rise to similar connections and a unique profile of the principal eigen spectra for each repeating unit. The efficacy of the approach is shown on eight repeat families annotated in UniProt, comprising of both solenoid and nonsolenoid repeats with varied secondary structure architecture and repeat lengths. The performance of the approach is also tested on other known benchmark datasets and the performance compared with two repeat identification methods. For a known repeat type, the algorithm also identifies the type of repeat present in the protein. A web tool implementing the algorithm is available at the URL http://bioinf.iiit.ac.in/PRIGSA/.

  16. Ataxin-2 repeat-length variation and neurodegeneration

    PubMed Central

    Ross, Owen A.; Rutherford, Nicola J.; Baker, Matt; Soto-Ortolaza, Alexandra I.; Carrasquillo, Minerva M.; DeJesus-Hernandez, Mariely; Adamson, Jennifer; Li, Ma; Volkening, Kathryn; Finger, Elizabeth; Seeley, William W.; Hatanpaa, Kimmo J.; Lomen-Hoerth, Catherine; Kertesz, Andrew; Bigio, Eileen H.; Lippa, Carol; Woodruff, Bryan K.; Knopman, David S.; White, Charles L.; Van Gerpen, Jay A.; Meschia, James F.; Mackenzie, Ian R.; Boylan, Kevin; Boeve, Bradley F.; Miller, Bruce L.; Strong, Michael J.; Uitti, Ryan J.; Younkin, Steven G.; Graff-Radford, Neill R.; Petersen, Ronald C.; Wszolek, Zbigniew K.; Dickson, Dennis W.; Rademakers, Rosa

    2011-01-01

    Expanded glutamine repeats of the ataxin-2 (ATXN2) protein cause spinocerebellar ataxia type 2 (SCA2), a rare neurodegenerative disorder. More recent studies have suggested that expanded ATXN2 repeats are a genetic risk factor for amyotrophic lateral sclerosis (ALS) via an RNA-dependent interaction with TDP-43. Given the phenotypic diversity observed in SCA2 patients, we set out to determine the polymorphic nature of the ATXN2 repeat length across a spectrum of neurodegenerative disorders. In this study, we genotyped the ATXN2 repeat in 3919 neurodegenerative disease patients and 4877 healthy controls and performed logistic regression analysis to determine the association of repeat length with the risk of disease. We confirmed the presence of a significantly higher number of expanded ATXN2 repeat carriers in ALS patients compared with healthy controls (OR = 5.57; P= 0.001; repeat length >30 units). Furthermore, we observed significant association of expanded ATXN2 repeats with the development of progressive supranuclear palsy (OR = 5.83; P= 0.004; repeat length >30 units). Although expanded repeat carriers were also identified in frontotemporal lobar degeneration, Alzheimer's and Parkinson's disease patients, these were not significantly more frequent than in controls. Of note, our study identified a number of healthy control individuals who harbor expanded repeat alleles (31–33 units), which suggests caution should be taken when attributing specific disease phenotypes to these repeat lengths. In conclusion, our findings confirm the role of ATXN2 as an important risk factor for ALS and support the hypothesis that expanded ATXN2 repeats may predispose to other neurodegenerative diseases, including progressive supranuclear palsy. PMID:21610160

  17. Repeated-sprint and effort ability in rugby league players.

    PubMed

    Johnston, Rich D; Gabbett, Tim J

    2011-10-01

    The aim of this study was to (a) investigate the influence of tackling on repeated-sprint performance; (b) determine whether repeated-sprint ability (RSA) and repeated-effort ability (REA) are 2 distinct qualities; and (c) assess the test-retest reliability of repeated-sprint and repeated-effort tests in rugby league. Twelve rugby league players performed a repeated-sprint (12 × 20-m sprints performed on a 20-second cycle) and a repeated-effort (12 × 20-m sprints with intermittent tackling, performed on a 20-second cycle) test 7 days apart. The test-retest reliability of these tests was also established. Heart rate and rating of perceived exertion were recorded throughout the tests. There was a significantly greater (p ≤ 0.05) and large effect size (ES) differences for total sprint time (ES = 1.19), average heart rate (ES = 1.64), peak heart rate (ES = 1.35), and perceived exertion (ES = 3.39) for the repeated-effort test compared with the repeated-sprint test. A large difference (ES = 1.02, p = 0.06) was detected for percentage decrement between the 2 tests. No significant relationship was found between the repeated-sprint and repeated-effort tests for any of the dependent variables. Both tests proved reliable, with total sprint time being the most reliable method of assessing performance. This study demonstrates that the addition of tackling significantly increases the physiological response to repeated-sprint exercise and reduces repeated-sprint performance in rugby league players. Furthermore, RSA and REA appear to be 2 distinct qualities that can be reliably assessed with total time being the most reliable measure of performance.

  18. Regeneration of Human Liver After Hepatic Lobectomy Studied by Repeated Liver Scanning and Repeated Needle Biopsy

    PubMed Central

    Lin, Tien-Yu; Lee, Chue-Shue; Chen, Chiou-Chiang; Liau, Kuong-Yi; Lin, Wen-Shih-Jen

    1979-01-01

    Regeneration of the residual lobe of the liver after hepatic lobectomy in humans was studied by repeated liver scanning in seven noncirrhotic and three cirrhotic patients. Each patient was studied for several months during the study which lasted from 1-12 years. Regeneration was apparent in noncirrhotic liver remnants following hepatic lobectomy. In the case of a long standing, space occupying lesions such as benign giant cysts, the liver remnant would complete its regeneration process rather early, usually within a few months of hepatic lobectomy. In hepatoma cases, however, regeneration of the residual lobe after hepatic resection usually took five or six months for completion. On the contrary, no definite increase in the size of the liver remnant was seen on repeated liver scanning in cirrhotic patients. Histologic study of the residual lobe was repeated on needle biopsy specimens in two noncirrhotic and four cirrhotic patients. Regenerative hyperplasia of liver cells with large hyperchromatic, or double nuclei never seen in the preresection liver appeared in the liver remnant five, 11, and 27 days after hepatic lobectomy in noncirrhotic patients. In cirrhotics, however, there were no histologic changes between the preresection liver and the postresection remnant studied three, five, 15, 40 days or even two years and 8 months after hepatic lobectomy. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6. PMID:464678

  19. Hydrological Modeling and Repeatability with Brokering

    NASA Astrophysics Data System (ADS)

    Easton, Z. M.; Collick, A.; Srinivasan, R.; Braeckel, A.; Nativi, S.; McAlister, C.; Wright, D. J.; Khalsa, S. J. S.; Fuka, D.

    2014-12-01

    Data brokering aims to provide those in the hydrological sciences with access to relevant data to represent physical, biological, and chemical characteristics researchers need to accelerate discovery in their domain. Environmental models are useful tools to understand the behavior of hydrological systems. Unfortunately, parameterization of these models requires many different data sources from different disciplines (e.g., atmospheric, geoscience, ecology). In hydrological modeling, the traditional procedure for model initialization starts with obtaining elevation models, land-use characterizations, soils maps, and weather data. It is often the researcher's past experience with these datasets that determines which datasets will be used in a study, and often newer, more suitable data products exist. An added complexity is that various science communities have differing data formats, storage protocols and manipulation methods, which makes use by a non domain scientist difficult and time consuming. We propose data brokering as a means to address several of these challenges. We present two test case scenarios in which researchers attempt to reproduce hydrological model results using 1) general internet based data gathering techniques, and 2) a scientific data brokering interface. We show that data brokering increases the efficiency with which data are collected, models are initialized, and results are analyzed. As an added benefit, it appears brokering significantly increases the repeatability of a study.

  20. Superfamily of ankyrin repeat proteins in tomato.

    PubMed

    Yuan, Xiaowei; Zhang, Shizhong; Qing, Xiaohe; Sun, Meihong; Liu, Shiyang; Su, Hongyan; Shu, Huairui; Li, Xinzheng

    2013-07-10

    The ankyrin repeat (ANK) protein family plays a crucial role in plant growth and development and in response to biotic and abiotic stresses. However, no detailed information concerning this family is available for tomato (Solanum lycopersicum) due to the limited information on whole genome sequences. In this study, we identified a total of 130 ANK genes in tomato genome (SlANK), and these genes were distributed across all 12 chromosomes at various densities. And chromosomal localizations of SlANK genes indicated 25 SlANK genes were involved in tandem duplications. Based on their domain composition, all of the SlANK proteins were grouped into 13 subgroups. A combined phylogenetic tree was constructed with the aligned SlANK protein sequences. This tree revealed that the SlANK proteins comprise five major groups. An analysis of the expression profiles of SlANK genes in tomato in different tissues and in response to stresses showed that the SlANK proteins play roles in plant growth, development and stress responses. To our knowledge, this is the first report of a genome-wide analysis of the tomato ANK gene family. This study provides valuable information regarding the classification and putative functions of SlANK genes in tomato.

  1. Repeat mitral valve replacement: 30-years' experience.

    PubMed

    Expósito, Víctor; García-Camarero, Tamara; Bernal, José M; Arnáiz, Elena; Sarralde, Aurelio; García, Iván; Berrazueta, José R; Revuelta, José M

    2009-08-01

    Prosthetic heart valve dysfunction is an acquired condition that carries a significant risk of emergency surgery. However, the long-term natural history of the condition is not well understood. Between 1974 and 2006, 1535 isolated mitral valve replacements were performed at our hospital (in-hospital mortality 5%). In total, 369 patients needed a second operation (in-hospital mortality 8.1%), while 80 (age 59.8+/-11.4 years) needed a third. The reasons for the third intervention were structural deterioration (67.5%), paravalvular leak (20%) and endocarditis (6.3%). Some 15 patients died in hospital (18.8%). After a mean follow-up period of 17.8 years, 21 patients needed another intervention (i.e., a fourth intervention). The actuarial reoperation-free rate at 20 years was 40.1+/-13.8%. The late mortality rate was 58.5% (18-year survival rate 15.4+/-5.4%). Indications for repeat mitral valve replacement must be judged on an individual basis given the high risk associated with surgery.

  2. Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency.

    PubMed

    Hoyos, Luis R; Thakur, Mili

    2016-12-19

    Fragile X premutation carriers have 55-200 CGG repeats in the 5' untranslated region of the FMR1 gene. Women with this premutation face many physical and emotional challenges in their life. Approximately 20% of these women will develop fragile X-associated primary ovarian insufficiency (FXPOI). In addition, they suffer from increased rates of menstrual dysfunction, diminished ovarian reserve, reduction in age of menopause, infertility, dizygotic twinning, and risk of having an offspring with a premutation or full mutation. Consequent chronic hypoestrogenism may result in impaired bone health and increased cardiovascular risk. Neuropsychiatric issues include risk of developing fragile X-associated tremor/ataxia syndrome, neuropathy, musculoskeletal problems, increased prevalence of anxiety, depression, and sleep disturbances independent of the stress of raising an offspring with fragile X syndrome and higher risk of postpartum depression. Some studies have reported a higher prevalence of thyroid abnormalities and hypertension in these women. Reproductive health providers play an important role in the health supervision of women with fragile X premutation. Awareness of these risks and correlation of the various manifestations could help in early diagnosis and coordination of care and services for these women and their families. This paper reviews current evidence regarding the possible conditions that may present in women with premutation-sized repeats beyond FXPOI.

  3. Hypoxic Repeat Sprint Training Improves Rugby Player's Repeated Sprint but Not Endurance Performance.

    PubMed

    Hamlin, Michael J; Olsen, Peter D; Marshall, Helen C; Lizamore, Catherine A; Elliot, Catherine A

    2017-01-01

    This study aims to investigate the performance changes in 19 well-trained male rugby players after repeat-sprint training (six sessions of four sets of 5 × 5 s sprints with 25 s and 5 min of active recovery between reps and sets, respectively) in either normobaric hypoxia (HYP; n = 9; FIO2 = 14.5%) or normobaric normoxia (NORM; n = 10; FIO2 = 20.9%). Three weeks after the intervention, 2 additional repeat-sprint training sessions in hypoxia (FIO2 = 14.5%) was investigated in both groups to gauge the efficacy of using "top-up" sessions for previously hypoxic-trained subjects and whether a small hypoxic dose would be beneficial for the previously normoxic-trained group. Repeated sprint (8 × 20 m) and Yo-Yo Intermittent Recovery Level 1 (YYIR1) performances were tested twice at baseline (Pre 1 and Pre 2) and weekly after (Post 1-3) the initial intervention (intervention 1) and again weekly after the second "top-up" intervention (Post 4-5). After each training set, heart rate, oxygen saturation, and rate of perceived exertion were recorded. Compared to baseline (mean of Pre 1 and Pre 2), both the hypoxic and normoxic groups similarly lowered fatigue over the 8 sprints 1 week after the intervention (Post 1: -1.8 ± 1.6%, -1.5 ± 1.4%, mean change ± 90% CI in HYP and NORM groups, respectively). However, from Post 2 onwards, only the hypoxic group maintained the performance improvement compared to baseline (Post 2: -2.1 ± 1.8%, Post 3: -2.3 ± 1.7%, Post 4: -1.9 ± 1.8%, and Post 5: -1.2 ± 1.7%). Compared to the normoxic group, the hypoxic group was likely to have substantially less fatigue at Post 3-5 (-2.0 ± 2.4%, -2.2 ± 2.4%, -1.6 ± 2.4% Post 3, Post 4, Post 5, respectively). YYIR1 performances improved throughout the recovery period in both groups (13-37% compared to baseline) with unclear differences found between groups. The addition of two sessions of "top-up" training after intervention 1, had little effect on either group. Repeat-sprint training in

  4. Hypoxic Repeat Sprint Training Improves Rugby Player's Repeated Sprint but Not Endurance Performance

    PubMed Central

    Hamlin, Michael J.; Olsen, Peter D.; Marshall, Helen C.; Lizamore, Catherine A.; Elliot, Catherine A.

    2017-01-01

    This study aims to investigate the performance changes in 19 well-trained male rugby players after repeat-sprint training (six sessions of four sets of 5 × 5 s sprints with 25 s and 5 min of active recovery between reps and sets, respectively) in either normobaric hypoxia (HYP; n = 9; FIO2 = 14.5%) or normobaric normoxia (NORM; n = 10; FIO2 = 20.9%). Three weeks after the intervention, 2 additional repeat-sprint training sessions in hypoxia (FIO2 = 14.5%) was investigated in both groups to gauge the efficacy of using “top-up” sessions for previously hypoxic-trained subjects and whether a small hypoxic dose would be beneficial for the previously normoxic-trained group. Repeated sprint (8 × 20 m) and Yo-Yo Intermittent Recovery Level 1 (YYIR1) performances were tested twice at baseline (Pre 1 and Pre 2) and weekly after (Post 1–3) the initial intervention (intervention 1) and again weekly after the second “top-up” intervention (Post 4–5). After each training set, heart rate, oxygen saturation, and rate of perceived exertion were recorded. Compared to baseline (mean of Pre 1 and Pre 2), both the hypoxic and normoxic groups similarly lowered fatigue over the 8 sprints 1 week after the intervention (Post 1: −1.8 ± 1.6%, −1.5 ± 1.4%, mean change ± 90% CI in HYP and NORM groups, respectively). However, from Post 2 onwards, only the hypoxic group maintained the performance improvement compared to baseline (Post 2: −2.1 ± 1.8%, Post 3: −2.3 ± 1.7%, Post 4: −1.9 ± 1.8%, and Post 5: −1.2 ± 1.7%). Compared to the normoxic group, the hypoxic group was likely to have substantially less fatigue at Post 3–5 (−2.0 ± 2.4%, −2.2 ± 2.4%, −1.6 ± 2.4% Post 3, Post 4, Post 5, respectively). YYIR1 performances improved throughout the recovery period in both groups (13–37% compared to baseline) with unclear differences found between groups. The addition of two sessions of “top-up” training after intervention 1, had little effect on either

  5. Repeating microearthquake sequences interact predominantly through postseismic slip

    NASA Astrophysics Data System (ADS)

    Lui, Semechah K. Y.; Lapusta, Nadia

    2016-10-01

    Studying small repeating earthquakes enables better understanding of fault physics and characterization of fault friction properties. Some of the nearby repeating sequences appear to interact, such as the `San Francisco' and `Los Angeles' repeaters on the creeping section of the San Andreas Fault. It is typically assumed that such interactions are induced by static stress changes due to coseismic slip. Here we present a study of the interaction of repeating earthquakes in the framework of rate-and-state fault models using state-of-the-art simulation methods that reproduce both realistic seismic events and long-term earthquake sequences. Our simulations enable comparison among several types of stress transfer that occur between the repeating events. Our major finding is that postseismic creep dominates the interaction, with earthquake triggering occurring at distances much larger than typically assumed. Our results open a possibility of using interaction of repeating sequences to constrain friction properties of creeping segments.

  6. Repeats in transforming acidic coiled-coil (TACC) genes.

    PubMed

    Trivedi, Seema

    2013-06-01

    Transforming acidic coiled-coil proteins (TACC1, 2, and 3) are essential proteins associated with the assembly of spindle microtubules and maintenance of bipolarity. Dysregulation of TACCs is associated with tumorigenesis, but studies of microsatellite instability in TACC genes have not been extensive. Microsatellite or simple sequence repeat instability is known to cause many types of cancer. The present in silico analysis of SSRs in human TACC gene sequences shows the presence of mono- to hexa-nucleotide repeats, with the highest densities found for mono- and di-nucleotide repeats. Density of repeats is higher in introns than in exons. Some of the repeats are present in regulatory regions and retained introns. Human TACC genes show conservation of many repeat classes. Microsatellites in TACC genes could be valuable markers for monitoring numerical chromosomal aberrations and or cancer.

  7. Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis.

    PubMed

    Buhard, Olivier; Suraweera, Nirosha; Lectard, Aude; Duval, Alex; Hamelin, Richard

    2004-01-01

    Microsatellite instability (MSI) analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats) to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability.

  8. Quasimonomorphic Mononucleotide Repeats for High-Level Microsatellite Instability Analysis

    PubMed Central

    Buhard, Olivier; Suraweera, Nirosha; Lectard, Aude; Duval, Alex; Hamelin, Richard

    2004-01-01

    Microsatellite instability (MSI) analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats) to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability. PMID:15528790

  9. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting.

    PubMed

    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F; Ignatova, Zoya

    2016-08-26

    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5' end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1.

  10. Survey of simple sequence repeats in woodland strawberry (Fragaria vesca).

    PubMed

    Guan, L; Huang, J F; Feng, G Q; Wang, X W; Wang, Y; Chen, B Y; Qiao, Y S

    2013-07-30

    The use of simple sequence repeats (SSRs), or microsatellites, as genetic markers has become popular due to their abundance and variation in length among individuals. In this study, we investigated linkage groups (LGs) in the woodland strawberry (Fragaria vesca) and demonstrated variation in the abundances, densities, and relative densities of mononucleotide, dinucleotide, and trinucleotide repeats. Mononucleotide, dinucleotide, and trinucleotide repeats were more common than longer repeats in all LGs examined. Perfect SSRs were the predominant SSR type found and their abundance was extremely stable among LGs and chloroplasts. Abundances of mononucleotide, dinucleotide, and trinucleotide repeats were positively correlated with LG size, whereas those of tetranucleotide and hexanucleotide SSRs were not. Generally, in each LG, the abundance, relative abundance, relative density, and the proportion of each unique SSR all declined rapidly as the repeated unit increased. Furthermore, the lengths and frequencies of SSRs varied among different LGs.

  11. Repeating microearthquake sequences interact predominantly through postseismic slip

    PubMed Central

    Lui, Semechah K. Y.; Lapusta, Nadia

    2016-01-01

    Studying small repeating earthquakes enables better understanding of fault physics and characterization of fault friction properties. Some of the nearby repeating sequences appear to interact, such as the ‘San Francisco' and ‘Los Angeles' repeaters on the creeping section of the San Andreas Fault. It is typically assumed that such interactions are induced by static stress changes due to coseismic slip. Here we present a study of the interaction of repeating earthquakes in the framework of rate-and-state fault models using state-of-the-art simulation methods that reproduce both realistic seismic events and long-term earthquake sequences. Our simulations enable comparison among several types of stress transfer that occur between the repeating events. Our major finding is that postseismic creep dominates the interaction, with earthquake triggering occurring at distances much larger than typically assumed. Our results open a possibility of using interaction of repeating sequences to constrain friction properties of creeping segments. PMID:27703151

  12. Repeating microearthquake sequences interact predominantly through postseismic slip.

    PubMed

    Lui, Semechah K Y; Lapusta, Nadia

    2016-10-05

    Studying small repeating earthquakes enables better understanding of fault physics and characterization of fault friction properties. Some of the nearby repeating sequences appear to interact, such as the 'San Francisco' and 'Los Angeles' repeaters on the creeping section of the San Andreas Fault. It is typically assumed that such interactions are induced by static stress changes due to coseismic slip. Here we present a study of the interaction of repeating earthquakes in the framework of rate-and-state fault models using state-of-the-art simulation methods that reproduce both realistic seismic events and long-term earthquake sequences. Our simulations enable comparison among several types of stress transfer that occur between the repeating events. Our major finding is that postseismic creep dominates the interaction, with earthquake triggering occurring at distances much larger than typically assumed. Our results open a possibility of using interaction of repeating sequences to constrain friction properties of creeping segments.

  13. Tandem repeats discovery service (TReaDS) applied to finding novel cis-acting factors in repeat expansion diseases

    PubMed Central

    2012-01-01

    Background Tandem repeats are multiple duplications of substrings in the DNA that occur contiguously, or at a short distance, and may involve some mutations (such as substitutions, insertions, and deletions). Tandem repeats have been extensively studied also for their association with the class of repeat expansion diseases (mostly affecting the nervous system). Comparative studies on the output of different tools for finding tandem repeats highlighted significant differences among the sets of detected tandem repeats, while many authors pointed up how critical it is the right choice of parameters. Results In this paper we present TReaDS - Tandem Repeats Discovery Service, a tandem repeat meta search engine. TReaDS forwards user requests to several state of the art tools for finding tandem repeats and merges their outcome into a single report, providing a global, synthetic, and comparative view of the results. In particular, TReaDS allows the user to (i) simultaneously run different algorithms on the same data set, (ii) choose for each algorithm a different setting of parameters, and (iii) obtain a report that can be downloaded for further, off-line, investigations. We used TReaDS to investigate sequences associated with repeat expansion diseases. Conclusions By using the tool TReaDS we discover that, for 27 repeat expansion diseases out of a currently known set of 29, long fuzzy tandem repeats are covering the expansion loci. Tests with control sets confirm the specificity of this association. This finding suggests that long fuzzy tandem repeats can be a new class of cis-acting elements involved in the mechanisms leading to the expansion instability. We strongly believe that biologists can be interested in a tool that, not only gives them the possibility of using multiple search algorithm at the same time, with the same effort exerted in using just one of the systems, but also simplifies the burden of comparing and merging the results, thus expanding our

  14. Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes

    PubMed Central

    Richard, Guy-Franck; Kerrest, Alix; Dujon, Bernard

    2008-01-01

    Summary: Repeated elements can be widely abundant in eukaryotic genomes, composing more than 50% of the human genome, for example. It is possible to classify repeated sequences into two large families, “tandem repeats” and “dispersed repeats.” Each of these two families can be itself divided into subfamilies. Dispersed repeats contain transposons, tRNA genes, and gene paralogues, whereas tandem repeats contain gene tandems, ribosomal DNA repeat arrays, and satellite DNA, itself subdivided into satellites, minisatellites, and microsatellites. Remarkably, the molecular mechanisms that create and propagate dispersed and tandem repeats are specific to each class and usually do not overlap. In the present review, we have chosen in the first section to describe the nature and distribution of dispersed and tandem repeats in eukaryotic genomes in the light of complete (or nearly complete) available genome sequences. In the second part, we focus on the molecular mechanisms responsible for the fast evolution of two specific classes of tandem repeats: minisatellites and microsatellites. Given that a growing number of human neurological disorders involve the expansion of a particular class of microsatellites, called trinucleotide repeats, a large part of the recent experimental work on microsatellites has focused on these particular repeats, and thus we also review the current knowledge in this area. Finally, we propose a unified definition for mini- and microsatellites that takes into account their biological properties and try to point out new directions that should be explored in a near future on our road to understanding the genetics of repeated sequences. PMID:19052325

  15. Repeated fecal microbiota transplantation in a child with ulcerative colitis.

    PubMed

    Shimizu, Hirotaka; Arai, Katsuhiro; Abe, Jun; Nakabayashi, Kazuhiko; Yoshioka, Takako; Hosoi, Kenji; Kuroda, Makoto

    2016-08-01

    We report the case of an 11-year-old girl with ulcerative colitis refractory to conventional therapy, who was subsequently treated successfully with repeated fecal microbiota transplantation (FMT). The patient was steroid dependent despite several infliximab treatments, and colectomy was proposed to improve quality of life. After repeated FMT, she was able to maintain remission with on minimal dose of steroid. Although her fecal microbiota was dysbiotic before FMT, it was restored to a similar pattern as the donor after repeated FMT.

  16. Diverse functions of WD40 repeat proteins in histone recognition

    PubMed Central

    Suganuma, Tamaki; Pattenden, Samantha G.; Workman, Jerry L.

    2008-01-01

    WD40 repeat proteins have been shown to bind the histone H3 tail at the center of their β-propeller structure. In contrast, in this issue of Genes & Development, Song and colleagues (pp. 1313–1318) demonstrate that the WD40 repeat protein p55 binds a structured region of H4 through a novel binding pocket on the side of β-propeller, illustrating a diversity of histone recognition by WD40 repeat proteins. PMID:18483215

  17. Artificial leucine rich repeats as new scaffolds for protein design.

    PubMed

    Baabur-Cohen, Hemda; Dayalan, Subashini; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2011-04-15

    The leucine rich repeat (LRR) motif that participates in many biomolecular recognition events in cells was suggested as a general scaffold for producing artificial receptors. We describe here the design and first total chemical synthesis of small LRR proteins, and their structural analysis. When evaluating the tertiary structure as a function of different number of repeating units (1-3), we were able to find that the 3-repeats sequence, containing 90 amino acids, folds into the expected structure.

  18. Assembly of Repeat Content Using Next Generation Sequencing Data

    SciTech Connect

    labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex

    2014-03-17

    Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

  19. [Repeated head injury during judo practice].

    PubMed

    Fujiwara, Kazue

    2014-01-01

    Mild traumatic brain injuries, if repeated, can cause permanent brain damage, or even death. I examined five published documents(three judicial decisions, one official injury report, and one book)to analyze incidents in which high school students who, while practicing judo, experienced acute subdural hematoma(ASDH)with grave outcomes, despite the fact that they had been examined by neurosurgeons. The five students, first-grade boy and girl of junior high school and two first-grade boys and one second-grade girl of senior high school, were hit on the head during extracurricular judo practice and were taken to the neurosurgery department of different hospitals. They were all novices or unskilled players. The initial diagnoses were ASDH in three cases, concussion in one, and headache in one. Although the surgeons, except in one case, prohibited the students from returning to play, the juveniles resumed judo practice soon. Some of them complained of continued headaches, but they kept practicing. Between 17 and 82 days after the first injury, they received the fateful hits to their heads, and they were brought to the emergency rooms. MRI and CT revealed ASDH in all;two of them died, and the other three remain in persistent vegetative state. Neurosurgeons should take the initiative to prevent severe brain injury of young athletes through collaborations with the athletes themselves, fellow athletes, family members, coaches, teachers, athletic directors, and other physicians. They should pay close attention to headaches and other signs and symptoms of concussion and prohibit the athletes from returning to play until they are confirmed to be symptom free for recommended periods, insisting that safety comes first.

  20. Simple sequence repeats in prokaryotic genomes

    PubMed Central

    Mrázek, Jan; Guo, Xiangxue; Shah, Apurva

    2007-01-01

    Simple sequence repeats (SSRs) in DNA sequences are composed of tandem iterations of short oligonucleotides and may have functional and/or structural properties that distinguish them from general DNA sequences. They are variable in length because of slip-strand mutations and may also affect local structure of the DNA molecule or the encoded proteins. Long SSRs (LSSRs) are common in eukaryotes but rare in most prokaryotes. In pathogens, SSRs can enhance antigenic variance of the pathogen population in a strategy that counteracts the host immune response. We analyze representations of SSRs in >300 prokaryotic genomes and report significant differences among different prokaryotes as well as among different types of SSRs. LSSRs composed of short oligonucleotides (1–4 bp length, designated LSSR1–4) are often found in host-adapted pathogens with reduced genomes that are not known to readily survive in a natural environment outside the host. In contrast, LSSRs composed of longer oligonucleotides (5–11 bp length, designated LSSR5–11) are found mostly in nonpathogens and opportunistic pathogens with large genomes. Comparisons among SSRs of different lengths suggest that LSSR1–4 are likely maintained by selection. This is consistent with the established role of some LSSR1–4 in enhancing antigenic variance. By contrast, abundance of LSSR5–11 in some genomes may reflect the SSRs' general tendency to expand rather than their specific role in the organisms' physiology. Differences among genomes in terms of SSR representations and their possible interpretations are discussed. PMID:17485665

  1. A Comparison of First Time and Repeat Rural DUI Offenders

    PubMed Central

    Dickson, Megan F.; Wasarhaley, Nesa E.; Webster, J. Matthew

    2015-01-01

    The purpose of the current study was to examine whether the differences found between first time and repeat rural DUI offenders were the same as those found previously in urban samples. A total of 118 rural DUI offenders were interviewed, approximately half (51.7%) of which were repeat offenders. Although demographic and mental health characteristics were similar across the two groups, repeat offenders reported more extensive substance use and criminal histories. Results suggest that the pattern of differences between rural first time and repeat DUI offenders may be different from the pattern found in prior urban-based studies. Treatment implications are discussed. PMID:26225118

  2. A Comparison of First Time and Repeat Rural DUI Offenders.

    PubMed

    Dickson, Megan F; Wasarhaley, Nesa E; Webster, J Matthew

    The purpose of the current study was to examine whether the differences found between first time and repeat rural DUI offenders were the same as those found previously in urban samples. A total of 118 rural DUI offenders were interviewed, approximately half (51.7%) of which were repeat offenders. Although demographic and mental health characteristics were similar across the two groups, repeat offenders reported more extensive substance use and criminal histories. Results suggest that the pattern of differences between rural first time and repeat DUI offenders may be different from the pattern found in prior urban-based studies. Treatment implications are discussed.

  3. Rhythm Facilitates the Detection of Repeating Sound Patterns

    PubMed Central

    Rajendran, Vani G.; Harper, Nicol S.; Abdel-Latif, Khaled H. A.; Schnupp, Jan W. H.

    2016-01-01

    This study investigates the influence of temporal regularity on human listeners' ability to detect a repeating noise pattern embedded in statistically identical non-repeating noise. Human listeners were presented with white noise stimuli that either contained a frozen segment of noise that repeated in a temporally regular or irregular manner, or did not contain any repetition at all. Subjects were instructed to respond as soon as they detected any repetition in the stimulus. Pattern detection performance was best when repeated targets occurred in a temporally regular manner, suggesting that temporal regularity plays a facilitative role in pattern detection. A modulation filterbank model could account for these results. PMID:26858589

  4. Coexistence of 3G repeaters with LTE base stations.

    PubMed

    Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

    2013-01-01

    Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

  5. Impact of small repeat sequences on bacterial genome evolution.

    PubMed

    Delihas, Nicholas

    2011-01-01

    Intergenic regions of prokaryotic genomes carry multiple copies of terminal inverted repeat (TIR) sequences, the nonautonomous miniature inverted-repeat transposable element (MITE). In addition, there are the repetitive extragenic palindromic (REP) sequences that fold into a small stem loop rich in G-C bonding. And the clustered regularly interspaced short palindromic repeats (CRISPRs) display similar small stem loops but are an integral part of a complex genetic element. Other classes of repeats such as the REP2 element do not have TIRs but show other signatures. With the current availability of a large number of whole-genome sequences, many new repeat elements have been discovered. These sequences display diverse properties. Some show an intimate linkage to integrons, and at least one encodes a small RNA. Many repeats are found fused with chromosomal open reading frames, and some are located within protein coding sequences. Small repeat units appear to work hand in hand with the transcriptional and/or post-transcriptional apparatus of the cell. Functionally, they are multifaceted, and this can range from the control of gene expression, the facilitation of host/pathogen interactions, or stimulation of the mammalian immune system. The CRISPR complex displays dramatic functions such as an acquired immune system that defends against invading viruses and plasmids. Evolutionarily, mobile repeat elements may have influenced a cycle of active versus inactive genes in ancestral organisms, and some repeats are concentrated in regions of the chromosome where there is significant genomic plasticity. Changes in the abundance of genomic repeats during the evolution of an organism may have resulted in a benefit to the cell or posed a disadvantage, and some present day species may reflect a purification process. The diverse structure, eclectic functions, and evolutionary aspects of repeat elements are described.

  6. Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

    PubMed Central

    Huang, Shanshan; Yang, Su; Guo, Jifeng; Yan, Sen; Gaertig, Marta A.; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    SUMMARY In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knock-in mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases. PMID:26387956

  7. PCR-free digital minisatellite tandem repeat genotyping.

    PubMed

    Chen, Yuchao; Seo, Tae Seok

    2011-06-01

    We demonstrated a proof-of-concept for novel minisatellite tandem repeat typing, called PCR-free digital VNTR (variable number tandem repeat) typing, which is composed of three steps: a ligation reaction instead of PCR thermal cycling, magnetic bead-based solid-phase capture for purification, and an elongated sample stacking microcapillary electrophoresis (μCE) for sensitive digital coding of repeat number. We designed a 16-bp fluorescently labeled ligation probe which is complementary to a repeat unit of a biotinylated synthetic template mimicking the human D1S80 VNTR locus and is randomly hybridized with the minisatellite tandem repeats. A quick isothermal ligation reaction was followed to link the adjacent ligation probes on the DNA templates, and then the ligated products were purified by streptavidin-coated magnetic beads. After a denaturing step, a large amount of ligated products whose size difference was equivalent to the repeat unit were released and recovered. Through the elongated sample stacking μCE separation on a microdevice, the fluorescence signal of the ligated products was generated in the electropherogram and the peak number was directly counted which was exactly matched with the repeat number of VNTR locus. We could successfully identify the minisatellite tandem repeat number with only 5 fmol of DNA template in 30 min.

  8. 40 CFR 1610.2 - Repeated attorney misconduct, sanctions, hearings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Repeated attorney misconduct, sanctions, hearings. 1610.2 Section 1610.2 Protection of Environment CHEMICAL SAFETY AND HAZARD INVESTIGATION BOARD ADMINISTRATIVE INVESTIGATIONS § 1610.2 Repeated attorney misconduct, sanctions, hearings....

  9. Secret key rates for an encoded quantum repeater

    NASA Astrophysics Data System (ADS)

    Bratzik, Sylvia; Kampermann, Hermann; Bruß, Dagmar

    2014-03-01

    We investigate secret key rates for the quantum repeater using encoding [L. Jiang et al., Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325] and compare them to the standard repeater scheme by Briegel, Dür, Cirac, and Zoller. The former scheme has the advantage of a minimal consumption of classical communication. We analyze the trade-off in the secret key rate between the communication time and the required resources. For this purpose we introduce an error model for the repeater using encoding which allows for input Bell states with a fidelity smaller than one, in contrast to the model given by L. Jiang et al. [Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325]. We show that one can correct additional errors in the encoded connection procedure of this repeater and develop a suitable decoding algorithm. Furthermore, we derive the rate of producing entangled pairs for the quantum repeater using encoding and give the minimal parameter values (gate quality and initial fidelity) for establishing a nonzero secret key. We find that the generic quantum repeater is optimal regarding the secret key rate per memory per second and show that the encoded quantum repeater using the simple three-qubit repetition code can even have an advantage with respect to the resources compared to other recent quantum repeater schemes with encoding.

  10. Preschool Children's Memory for Repeated Changes in the Lunch Routine.

    ERIC Educational Resources Information Center

    Krackow, Elisa

    An experiment examined the possibilities that: (1) repeated deviations in a routine event become fused into the general event representation (GER) for that event; and (2) when deviations go unreported, it is because they have been forgotten. Preschool children were interviewed to get their script reports before and after repeated deviations in the…

  11. Repeated Reading, Turn Taking, and Augmentative and Alternative Communication (AAC)

    ERIC Educational Resources Information Center

    Edmister, Evette; Wegner, Jane

    2015-01-01

    This single participant multiple baseline research design measured the effects of repeatedly reading narrative books to children who used voice output augmentative communication devices to communicate. The study sought to determine if there was a difference observed in the number of turns taken when reading stories repeatedly. Three girls ranging…

  12. Intrinsic unsharpness and approximate repeatability of quantum measurements

    NASA Astrophysics Data System (ADS)

    Carmeli, Claudio; Heinonen, Teiko; Toigo, Alessandro

    2007-02-01

    The intrinsic unsharpness of a quantum observable is studied by introducing the notion of resolution width. This quantification of accuracy is shown to be closely connected with the possibility of making approximately repeatable measurements. As a case study, the intrinsic unsharpness and approximate repeatability of position and momentum measurements are examined in detail.

  13. Repeated Reading: Testing Alternative Models for Efficient Implementation

    ERIC Educational Resources Information Center

    Lewis, Greg

    2012-01-01

    An investigation was conducted to determine the best criterion for advancement to a new reading passage during the commonly used classroom strategy of repeated reading. Knowing when to move students to a new passage during the repeated reading process was considered of value to teachers in efficiently using student learning time. The study also…

  14. Absence of bacterial resistance following repeat exposure to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Pedigo, Lisa A.; Gibbs, Aaron J.; Scott, Robert J.; Street, Cale N.

    2009-06-01

    The prevalence of antibiotic resistant bacteria necessitates exploration of alternative approaches to treat hospital and community acquired infections. The aim of this study was to determine whether bacterial pathogens develop resistance to antimicrobial photodynamic therapy (aPDT) during repeated sub-lethal challenge. Antibiotic sensitive and resistant strains of S. aureus and antibiotic sensitive E. coli were subjected to repeat PDT treatments using a methylene blue photosensitizer formulation and 670 nm illumination from a non-thermal diode laser. Parameters were adjusted such that kills were <100% so that surviving colonies could be passaged for subsequent exposures. With each repeat, kills were compared to those using non-exposed cultures of the same strain. Oxacillin resistance was induced in S. aureus using a disc diffusion method. For each experiment, "virgin" and "repeat" cultures were exposed to methylene blue at 0.01% w/v and illuminated with an energy dose of 20.6 J/cm2. No significant difference in killing of E. coli (repeat vs. virgin culture) was observed through 11 repeat exposures. Similar results were seen using MSSA and MRSA, wherein kill rate did not significantly differ from control over 25 repeat exposures. In contrast, complete oxacillin resistance could be generated in S. aureus over a limited number of exposures. PDT is effective in the eradication of pathogens including antibiotic resistance strains. Furthermore, repeated sub-lethal exposure does not induce resistance to subsequent PDT treatments. The absence of resistance formation represents a significant advantage of PDT over traditional antibiotics.

  15. Contagion and Repeat Offending among Urban Juvenile Delinquents

    ERIC Educational Resources Information Center

    Mennis, Jeremy; Harris, Philip

    2011-01-01

    This research investigates the role of repeat offending and spatial contagion in juvenile delinquency recidivism using a database of 7166 male juvenile offenders sent to community-based programs by the Family Court of Philadelphia. Results indicate evidence of repeat offending among juvenile delinquents, particularly for drug offenders. The…

  16. UNSTABLE MUTATIONS IN THE FMR1 GENE AND THE PHENOTYPES

    PubMed Central

    Loesch, Danuta; Hagerman, Randi

    2014-01-01

    Fragile X syndrome (FXS), a severe neurodevelopmental anomaly, and one of the earliest disorders linked to an unstable (‘dynamic’) mutation, is caused by the large (>200) CGG repeat expansions in the noncoding portion of the FMR1 (Fragile X Mental Retardation-1) gene. These expansions, termed full mutations, normally silence this gene's promoter through methylation, leading to a gross deficit of the Fragile X Mental Retardation Protein (FMRP) that is essential for normal brain development. Rare individuals with the expansion but with an unmethylated promoter (and thus, FMRP production), present a much less severe form of FXS. However, a unique feature of the relationship between the different sizes of CGG expanded tract and phenotypic changes is that smaller expansions (<200) generate a series of different clinical manifestations and/or neuropsychological changes. The major part of this chapter is devoted to those FMR1 alleles with small (55-200) CGG expansions, termed ‘premutations’, which have the potential for generating the full mutation alleles on mother-offspring transmission, on the one hand, and are associated with some phenotypic changes, on the other. Thus, the role of several factors known to determine the rate of CGG expansion in the premutation alleles is discussed first. Then, an account of various neurodevelopmental, congnitive, behavioural and physical changes reported in carriers of these small expansions is given, and possible association of these conditions with a toxicity of the elevated FMR1 gene's transcript (mRNA) is discussed. The next two sections are devoted to major and well defined clinical conditions associated with the premutation alleles. The first one is the late onset neurodegenerative disorder termed fragile X-associated tremor ataxia syndrome (FXTAS). The wide range of clinical and neuropsychological manifestations of this syndrome, and their relevance to elevated levels of the FMR1 mRNA, are described. Another distinct

  17. Witness recall across repeated interviews in a case of repeated abuse.

    PubMed

    Brubacher, Sonja P; La Rooy, David

    2014-02-01

    In this illustrative case study we examine the three forensic interviews of a girl who experienced repeated sexual abuse from ages 7 to 11. She disclosed the abuse after watching a serialized television show that contained a storyline similar to her own experience. This triggered an investigation that ended in successful prosecution of the offender. Because this case involved abuse that was repeated on a weekly basis for 4 years we thus investigated the degree to which the child's narrative reflected specific episodes or generic accounts, and both the interviewer's and child's attempts to elicit and provide, respectively, specific details across the 3 interviews collected in a 1 month period. Across the 3 interviews, the child's account was largely generic, yet on a number of occasions she provided details specific to individual incidents (episodic leads) that could have been probed further. As predicted: earlier interviews were characterized more by episodic than generic prompts and the reverse was true for the third interview; the child often responded using the same style of language (episodic or generic) as the interviewer; and open questions yielded narrative information. We discuss the importance of adopting children's words to specify occurrences, and the potential benefits of permitting generic recall in investigative interviews on children's ability to provide episodic leads. Despite the fact that the testimony was characterized by generic information about what usually happened, rather than specific episodic details about individual occurrences, this case resulted in successful prosecution.

  18. Biochemical analysis of oligomerization of expanded polyalanine repeat proteins.

    PubMed

    Nojima, Jun; Oma, Yoko; Futai, Eugene; Sasagawa, Noboru; Kuroda, Reiko; Turk, Boris; Ishiura, Shoichi

    2009-08-01

    Many human proteins contain amino acid repeats that can form homopolymeric amino acid (HPAA) tracts. HPAA tract proteins that contain polyalanine sequences promote diseases, including oculopharyngeal muscular dystrophy. The pathological properties of these proteins develop when the repeats match or exceed approximately 20 residues. We analyzed the oligomerization of yellow fluorescent protein (YFP) and GST fusion proteins containing >20 alanine repeats by using sucrose density gradient centrifugation. YFP and GST fusion proteins having 23 polyalanine residues sedimented readily in sucrose density gradients, suggesting instability and oligomerization of proteins with an excess of 20 alanine repeats. Moreover, GST fusion proteins were resistant to trypsin digestion after oligomerization. Oligomerized artificial proteins with long polyalanine repeats may be suitable models for studying polyalanine-related diseases.

  19. Repeat proteins challenge the concept of structural domains.

    PubMed

    Espada, Rocío; Parra, R Gonzalo; Sippl, Manfred J; Mora, Thierry; Walczak, Aleksandra M; Ferreiro, Diego U

    2015-10-01

    Structural domains are believed to be modules within proteins that can fold and function independently. Some proteins show tandem repetitions of apparent modular structure that do not fold independently, but rather co-operate in stabilizing structural forms that comprise several repeat-units. For many natural repeat-proteins, it has been shown that weak energetic links between repeats lead to the breakdown of co-operativity and the appearance of folding sub-domains within an apparently regular repeat array. The quasi-1D architecture of repeat-proteins is crucial in detailing how the local energetic balances can modulate the folding dynamics of these proteins, which can be related to the physiological behaviour of these ubiquitous biological systems.

  20. Study of repeater technology for advanced multifunctional communications satellites

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Investigations are presented concerning design concepts and implementation approaches for the satellite communication repeater subsystems of advanced multifunctional satellites. In such systems the important concepts are the use of multiple antenna beams, repeater switching (routing), and efficient spectrum utilization through frequency reuse. An information base on these techniques was developed and tradeoff analyses were made of repeater design concepts, with the work design taken in a broad sense to include modulation beam coverage patterns. There were five major areas of study: requirements analysis and processing; study of interbeam interference in multibeam systems; characterization of multiple-beam switching repeaters; estimation of repeater weight and power for a number of alternatives; and tradeoff analyses based on these weight and power data.

  1. mreps: efficient and flexible detection of tandem repeats in DNA

    PubMed Central

    Kolpakov, Roman; Bana, Ghizlane; Kucherov, Gregory

    2003-01-01

    The presence of repeated sequences is a fundamental feature of genomes. Tandemly repeated DNA appears in both eukaryotic and prokaryotic genomes, it is associated with various regulatory mechanisms and plays an important role in genomic fingerprinting. In this paper, we describe mreps, a powerful software tool for a fast identification of tandemly repeated structures in DNA sequences. mreps is able to identify all types of tandem repeats within a single run on a whole genomic sequence. It has a resolution parameter that allows the program to identify ‘fuzzy’ repeats. We introduce main algorithmic solutions behind mreps, describe its usage, give some execution time benchmarks and present several case studies to illustrate its capabilities. The mreps web interface is accessible through http://www.loria.fr/mreps/. PMID:12824391

  2. Repeatability Evaluation of Finger Tapping Device with Magnetic Sensors

    NASA Astrophysics Data System (ADS)

    Sano, Yuko; Kandori, Akihiko; Shima, Keisuke; Tamura, Yasuhiro; Takagi, Hiroshi; Tsuji, Toshio; Noda, Masafumi; Higashikawa, Fumiko; Yokoe, Masaru; Sakoda, Saburo

    We tested the repeatability of a finger tapping device with magnetic sensors to determine its reliability. This device, which was developed to assist in the diagnosis of movement disorders such as Parkinson's disease (PD) and strokes, measures the distance between the first and index fingers during finger tapping movements (opening and closing the fingers repeatedly). We evaluated three types of repeatability based on ICC (interclass correlation coefficient) and Welch's test (test for equal means in a oneway layout): repeatability when measured at different times, when using different devices, and when using different measurers. We calculated these three types for three finger tapping tasks on both hands for 21 characteristics calculated from finger tapping waveforms. Results demonstrated that the repeatability when using different devices is high regardless of the task or hand. The repeatability when measuring at different times and when using different measurers is high at some tasks, but not all. One of the finger tapping tasks (finger tapping movement with the largest amplitude and highest velocity), which is used in a conventional PD diagnosis method (UPDRS), does not have enough repeatability, while other tasks show high repeatability. Results also showed that five characteristics have the highest repeatability (ICC ≥ 0.5 or significance probability of Welch's test ≥ 5% in all tasks): “total moving distance,” “average of local minimum acceleration in opening motion,” “average of local minimum acceleration in closing motion,” “average of local maximum distance” and “average of local minimum velocity”. These results clearly demonstrate the strong repeatability of this device and lead to more precise diagnosis of movement disorders.

  3. Repeating and not so Repeating Large Earthquakes in the Mexican Subduction Zone

    NASA Astrophysics Data System (ADS)

    Hjorleifsdottir, V.; Singh, S.; Iglesias, A.; Perez-Campos, X.

    2013-12-01

    The rupture area and recurrence interval of large earthquakes in the mexican subduction zone are relatively small and almost the entire length of the zone has experienced a large (Mw≥7.0) earthquake in the last 100 years (Singh et al., 1981). Several segments have experienced multiple large earthquakes in this time period. However, as the rupture areas of events prior to 1973 are only approximately known, the recurrence periods are uncertain. Large earthquakes occurred in the Ometepec, Guerrero, segment in 1937, 1950, 1982 and 2012 (Singh et al., 1981). In 1982, two earthquakes (Ms 6.9 and Ms 7.0) occurred about 4 hours apart, one apparently downdip from the other (Astiz & Kanamori, 1984; Beroza et al. 1984). The 2012 earthquake on the other hand had a magnitude of Mw 7.5 (globalcmt.org), breaking approximately the same area as the 1982 doublet, but with a total scalar moment about three times larger than the 1982 doublet combined. It therefore seems that 'repeat earthquakes' in the Ometepec segment are not necessarily very similar one to another. The Central Oaxaca segment broke in large earthquakes in 1928 (Mw7.7) and 1978 (Mw7.7) . Seismograms for the two events, recorded at the Wiechert seismograph in Uppsala, show remarkable similarity, suggesting that in this area, large earthquakes can repeat. The extent to which the near-trench part of the fault plane participates in the ruptures is not well understood. In the Ometepec segment, the updip portion of the plate interface broke during the 25 Feb 1996 earthquake (Mw7.1), which was a slow earthquake and produced anomalously low PGAs (Iglesias et al., 2003). Historical records indicate that a great tsunamigenic earthquake, M~8.6, occurred in the Oaxaca region in 1787, breaking the Central Oaxaca segment together with several adjacent segments (Suarez & Albini 2009). Whether the updip portion of the fault broke in this event remains speculative, although plausible based on the large tsunami. Evidence from the

  4. Triplet-repeat microsatellites shared among hard and soft pines.

    PubMed

    Kutil, B L; Williams, C G

    2001-01-01

    Vascular plant species have shown a low level of microsatellite conservation compared to many animal species. Finding trans-specific microsatellites for plants may be improved by using a priori knowledge of genome organization. Fifteen triplet-repeat microsatellites from hard pine (Pinus taeda L.) were tested for trans-specific amplification across seven hard pines (P. palustris Mill., P. echinata Mill., P. radiata D. Don., P. patula Schiede et Deppe, P. halepensis Mill., P. kesiya Royle), a soft pine (P. strobus L.), and Picea rubens Sargent. Seven of 15 microsatellites had trans-specific amplification in both hard and soft pine subgenera. Two P. taeda microsatellites had conserved flanking regions and repeat motifs in all seven hard pines, soft pine P. strobus, and P. rubens. Perfect triplet-repeat P. taeda microsatellites appear to be better candidates for trans-specific polymorphism than compound microsatellites. Not all perfect triplet-repeat microsatellites were conserved, but all conserved microsatellites had perfect repeat motifs. Persistent microsatellites PtTX2123 and PtTX3020 had highly conserved flanking regions and a conserved repeat motif composition with variable repeat unit numbers. Using trinucleotide microsatellites improved trans-specific microsatellite recovery among hard and soft pine species.

  5. Oxidative Stress Adaptation with Acute, Chronic and Repeated Stress

    PubMed Central

    Pickering, Andrew M.; Vojtovich, Lesya; Tower, John; Davies, Kelvin J. A.

    2013-01-01

    Oxidative stress adaptation or hormesis is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells, and the fruit fly Drosophila melanogaster, are capable of adapting to chronic or repeated stress by up-regulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12 hours or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the level of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila, nevertheless also caused significant reductions in lifespan for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life. PMID:23142766

  6. Exploring the repeat protein universe through computational protein design.

    PubMed

    Brunette, T J; Parmeggiani, Fabio; Huang, Po-Ssu; Bhabha, Gira; Ekiert, Damian C; Tsutakawa, Susan E; Hura, Greg L; Tainer, John A; Baker, David

    2015-12-24

    A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.

  7. Methods for analysing cardiovascular studies with repeated measures.

    PubMed

    Cleophas, T J; Zwinderman, A H; van Ouwerkerk, B M

    2009-11-01

    Background. Repeated measurements in a single subject are generally more similar than unrepeated measurements in different subjects. Unrepeated analyses of repeated data cause underestimation of the treatment effects.Objective. To review methods adequate for the analysis of cardiovascular studies with repeated measures.Results. (1) For between-subjects comparisons, summary measures and random-effects mixedlinear models are possible. Examples of summary measures include the area under the curve of drug time-concentration and time-efficacy curves, maximal values, mean values, and changes from baseline. A problem is that precision is lost because averages, rather than individual data, are applied. Random-effects mixed-linear models, available in SPSS statistical software and other software programmes, provide better precision for that purpose. (2) For within-subjects comparisons, repeated-measures ANOVAs are available in SPSS and other software programmes. Subgroup factors such as gender differences and age class can be included.Discussion. For non-Gaussian data, Wilcoxon's and Friedman's tests are available, for binary data McNemar's tests can be used in case of two repeated observations. No standard methods are available for repeated binary measures with more than two observations. The purpose of this review was not to present a complete report but, rather, to underline that ample efforts should be made to account for the special nature of repeated measures. (Neth Heart J 2009;17:429-33.).

  8. Environmental stress induces trinucleotide repeat mutagenesis in human cells

    PubMed Central

    Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A.; Yotnda, Patricia; Wilson, John H.

    2015-01-01

    The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)—the cause of multiple human diseases—have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential. PMID:25775519

  9. Signal Hill solar-powered repeater report and recommendations

    NASA Astrophysics Data System (ADS)

    Smith, G. R.

    1984-08-01

    The parially active repeater (PAR) discussed is the GTE Lenkurt 700C1 repeater. The 700C1 repeater is the first radio of its kind to operate in the 7/8 GHz frequency band. The 700C1's low power consumption makes it ideal to be powered by solar voltaic cells. A new PAR site costs substantially less to develop than a fully active repeater since less support equipment is needed, no a-c power has to be brought to the site, and the building can be as small as 6' x 6'. A prototype 700C1 solar powered repeater was installed to eventually replace the existing poor microwave path between Big Eddy Substation and Wasco Radio Station. The repeater's RF performance is better than BPA's original specifications. The solar panels did not generate power during the winter months, so additional solar panels were added in May 1982. The new microwave path between Wasco and Big Eddy, via Signal Hill, is a large improvement over the previous path, which was via a double passive repeater; noise levels were reduced and signal strength improved.

  10. Genomic repeats, genome plasticity and the dynamics of Mycoplasma evolution

    PubMed Central

    Rocha, Eduardo P. C.; Blanchard, Alain

    2002-01-01

    Mycoplasmas evolved by a drastic reduction in genome size, but their genomes contain numerous repeated sequences with important roles in their evolution. We have established a bioinformatic strategy to detect the major recombination hot-spots in the genomes of Mycoplasma pneumoniae, Mycoplasma genitalium, Ureaplasma urealyticum and Mycoplasma pulmonis. This allowed the identification of large numbers of potentially variable regions, as well as a comparison of the relative recombination potentials of different genomic regions. Different trends are perceptible among mycoplasmas, probably due to different functional and structural constraints. The largest potential for illegitimate recombination in M.pulmonis is found at the vsa locus and its comparison in two different strains reveals numerous changes since divergence. On the other hand, the main M.pneumoniae and M.genitalium adhesins rely on large distant repeats and, hence, homologous recombination for variation. However, the relation between the existence of repeats and antigenic variation is not necessarily straightforward, since repeats of P1 adhesin were found to be anti-correlated with epitopes recognized by patient antibodies. These different strategies have important consequences for the structures of genomes, since large distant repeats correlate well with the major chromosomal rearrangements. Probably to avoid such events, mycoplasmas strongly avoid inverse repeats, in comparison to co-oriented repeats. PMID:11972343

  11. The Unstable Repeats - Three Evolving Faces of Neurological Disease

    PubMed Central

    Nelson, David L.; Orr, Harry T.; Warren, Stephen T.

    2013-01-01

    Disorders characterized by expansion of an unstable nucleotide repeat account for a number of inherited neurological diseases. Here, we review examples of unstable repeat disorders that nicely illustrate the three of the major pathogenic mechanisms associated with these diseases: loss-of-function typically by disrupting transcription of the mutated gene, RNA toxic gain-of-function, and protein toxic gain-of-function. In addition to providing insight into the mechanisms underlying these devastating neurological disorders, the study of these unstable microsatellite repeat disorders has provided insight into very basic aspects of neuroscience. PMID:23473314

  12. Secure quantum network coding for controlled repeater networks

    NASA Astrophysics Data System (ADS)

    Shang, Tao; Li, Jiao; Liu, Jian-wei

    2016-07-01

    To realize efficient quantum communication based on quantum repeater, we propose a secure quantum network coding scheme for controlled repeater networks, which adds a controller as a trusted party and is able to control the process of EPR-pair distribution. As the key operations of quantum repeater, local operations and quantum communication are designed to adopt quantum one-time pad to enhance the function of identity authentication instead of local operations and classical communication. Scheme analysis shows that the proposed scheme can defend against active attacks for quantum communication and realize long-distance quantum communication with minimal resource consumption.

  13. Large tandem, higher order repeats and regularly dispersed repeat units contribute substantially to divergence between human and chimpanzee Y chromosomes.

    PubMed

    Paar, Vladimir; Glunčić, Matko; Basar, Ivan; Rosandić, Marija; Paar, Petar; Cvitković, Mislav

    2011-01-01

    Comparison of human and chimpanzee genomes has received much attention, because of paramount role for understanding evolutionary step distinguishing us from our closest living relative. In order to contribute to insight into Y chromosome evolutionary history, we study and compare tandems, higher order repeats (HORs), and regularly dispersed repeats in human and chimpanzee Y chromosome contigs, using robust Global Repeat Map algorithm. We find a new type of long-range acceleration, human-accelerated HOR regions. In peripheral domains of 35mer human alphoid HORs, we find riddled features with ten additional repeat monomers. In chimpanzee, we identify 30mer alphoid HOR. We construct alphoid HOR schemes showing significant human-chimpanzee difference, revealing rapid evolution after human-chimpanzee separation. We identify and analyze over 20 large repeat units, most of them reported here for the first time as: chimpanzee and human ~1.6 kb 3mer secondary repeat unit (SRU) and ~23.5 kb tertiary repeat unit (~0.55 kb primary repeat unit, PRU); human 10848, 15775, 20309, 60910, and 72140 bp PRUs; human 3mer SRU (~2.4 kb PRU); 715mer and 1123mer SRUs (5mer PRU); chimpanzee 5096, 10762, 10853, 60523 bp PRUs; and chimpanzee 64624 bp SRU (10853 bp PRU). We show that substantial human-chimpanzee differences are concentrated in large repeat structures, at the level of as much as ~70% divergence, sizably exceeding previous numerical estimates for some selected noncoding sequences. Smeared over the whole sequenced assembly (25 Mb) this gives ~14% human-chimpanzee divergence. This is significantly higher estimate of divergence between human and chimpanzee than previous estimates.

  14. Optimum periodicity of repeated contractile actions applied in mass transport

    PubMed Central

    Ahn, Sungsook; Lee, Sang Joon

    2015-01-01

    Dynamically repeated periodic patterns are abundant in natural and artificial systems, such as tides, heart beats, stock prices, and the like. The characteristic repeatability and periodicity are expected to be optimized in effective system-specific functions. In this study, such optimum periodicity is experimentally evaluated in terms of effective mass transport using one-valve and multi-valve systems working in contractile fluid flows. A set of nanoscale gating functions is utilized, operating in nanocomposite networks through which permeates selectively pass under characteristic contractile actions. Optimized contractile periodicity exists for effective energy impartment to flow in a one-valve system. In the sequential contractile actions for a multi-valve system, synchronization with the fluid flow is critical for effective mass transport. This study provides fundamental understanding on the various repeated periodic patterns and dynamic repeatability occurring in nature and mechanical systems, which are useful for broad applications. PMID:25622949

  15. An optimal property of the repeated significance test

    PubMed Central

    Lerche, Hans Rudolf

    1986-01-01

    It is shown that the repeated significance test is a Bayes test for testing sequentially the sign of the drift of a Brownian motion. Its relation to Wald's sequential probability ratio test is studied. PMID:16593662

  16. An unusual case of repeated intracranial hemorrhage in vestibular schwannoma

    PubMed Central

    Banaama, Saeed; van Overbeeke, Jacobus; Temel, Yasin

    2016-01-01

    Background: Symptomatic intratumoral hemorrhage (ITH) in vestibular schwannoma (VS) is rare. A repeated hemorrhage is, therefore, even more exceptional. Repeated ITH has been reported in four cases thus far in English literature. Here, we describe a patient with a Koos grade D VS who presented to our Skull Base team with repeated ITH and an unexpected disease course. Case Description: A 76-year-old woman presented with hearing loss due to polycystic VS on the left side. Five years later, the patient was presented with facial palsy caused by hemorrhage in the VS. The patient had an eventful medical history that necessitated the use of anti-coagulants. The patient suffered from three subsequent hemorrhages preoperatively and one hemorrhage 36 h postoperatively. Conclusion: We have experienced multiple repeated hemorrhages in a patient with a polycystic VS, and despite surgical intervention, the outcome was unfavorable. PMID:27999710

  17. Correct use of repeated measures analysis of variance.

    PubMed

    Park, Eunsik; Cho, Meehye; Ki, Chang-Seok

    2009-02-01

    In biomedical research, researchers frequently use statistical procedures such as the t-test, standard analysis of variance (ANOVA), or the repeated measures ANOVA to compare means between the groups of interest. There are frequently some misuses in applying these procedures since the conditions of the experiments or statistical assumptions necessary to apply these procedures are not fully taken into consideration. In this paper, we demonstrate the correct use of repeated measures ANOVA to prevent or minimize ethical or scientific problems due to its misuse. We also describe the appropriate use of multiple comparison tests for follow-up analysis in repeated measures ANOVA. Finally, we demonstrate the use of repeated measures ANOVA by using real data and the statistical software package SPSS (SPSS Inc., USA).

  18. Repeatable measurements in quantum theory: Their role and feasibility

    SciTech Connect

    Busch, P.; Grabowski, M.; Lahti, P.J.

    1995-09-01

    Recent advantages in experimental quantum physics call for a careful reconsideration of the measurements process in quantum mechanics. In this paper we describe the structure of the ideal measurements and their status among the repeatable measurements. Then we provide an exhaustive account of the interrelations between repeatability and the apparently weaker notions of value reproducible or first-kind measurements. We demonstrate the close link between repeatable measurements and discrete observables and show how the ensuing measurement limitations for continuous observables can be lifted in a way that is in full accordance with actual experimental practice. We present examples of almost repeatable measurements of continuous observables and some realistic models of weakly disturbing measurements.

  19. Highly Informative Simple Sequence Repeat (SSR) Markers for Fingerprinting Hazelnut

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Simple sequence repeat (SSR) or microsatellite markers have many applications in breeding and genetic studies of plants, including fingerprinting of cultivars and investigations of genetic diversity, and therefore provide information for better management of germplasm collections. They are repeatab...

  20. Markerless modification of trinucleotide repeat loci in BACs.

    PubMed

    Benzow, Kellie A; Koob, Michael D

    2013-01-01

    Transcription and splicing of human genes are regulated by nucleotide sequences encoded across large segments of our genome, and trinucleotide repeat expansion mutations can have both profound and subtle effects on these processes. In the course of our work to understand the impact of the Spinocerebellar Ataxia type 8 (SCA8) CTG repeat expansion on the transcription and splicing of the RNAs encoded near the SCA8 locus, we have developed a set of reagents and protocols for modifying large genomic BAC clones of this region. We describe the two-step procedure that allows us to precisely replace unexpanded trinucleotide repeats with expanded variants of these repeat sequences without leaving any exogenous sequences in the final constructs, and we discuss how this approach can be adapted to make other desired sequence changes to these genomic clones.

  1. Impaired Mitochondrial Function and Dynamics in the Pathogenesis of FXTAS.

    PubMed

    Alvarez-Mora, M I; Rodriguez-Revenga, L; Madrigal, I; Guitart-Mampel, M; Garrabou, G; Milà, M

    2016-10-22

    Mitochondrial involvement plays an important role in neurodegenerative diseases. At least one-third of adult carriers of a FMR1 premutation (55-200 CGG repeats) are at risk of presenting an adult-onset neurodegenerative disorder known as fragile X-associated tremor/ataxia syndrome (FXTAS). In an attempt to provide new insights into the mechanisms involved in the pathogenesis of FXTAS, we characterized mitochondrial function and dynamics by the assessment of oxidative respiratory chain function, mitochondrial content, oxidative stress levels, and mitochondrial network complexity. Regarding mitochondrial function, we found that mitochondrial respiratory capacity is compromised in skin fibroblasts whereas in blood, no differences were observed between the FXTAS and control groups. Furthermore, fibroblasts from FXTAS patients presented altered mitochondrial architecture, with more circular and less interconnected mitochondria being observed. Mitochondrial function and dynamics deregulation and characteristic of neurological disorders are present in FXTAS patients. These features might be limiting temporal and spatial bioenergetics cells supply and thus contributing to disease pathogenesis.

  2. Fragile X-associated tremor/ataxia syndrome: An under-recognised cause of tremor and ataxia.

    PubMed

    Kalus, Sarah; King, John; Lui, Elaine; Gaillard, Frank

    2016-01-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive degenerative movement disorder resulting from a fragile X "premutation", defined as 55-200 CGG repeats in the 5'-untranslated region of the FMR1 gene. The FMR1 premutation occurs in 1/800 males and 1/250 females, with FXTAS affecting 40-45% of male and 8-16% of female premutation carriers over the age of 50. FXTAS typically presents with kinetic tremor and cerebellar ataxia. FXTAS has a classical imaging profile which, in concert with clinical manifestations and genetic testing, participates vitally in its diagnosis. The revised FXTAS diagnostic criteria include two major radiological features. The "MCP sign", referring to T2 hyperintensity in the middle cerebellar peduncle, has long been considered the radiological hallmark of FXTAS. Recently included as a major radiological criterion in the diagnosis of FXTAS is T2 hyperintensity in the splenium of the corpus callosum. Other imaging features of FXTAS include T2 hyperintensities in the pons, insula and periventricular white matter as well as generalised brain and cerebellar atrophy. FXTAS is an under-recognised and misdiagnosed entity. In patients with unexplained tremor, ataxia and cognitive decline, the presence of middle cerebellar peduncle and/or corpus callosum splenium hyperintensity should raise suspicion of FXTAS. Diagnosis of FXTAS has important implications not only for the patient but also, through genetic counselling and testing, for future generations.

  3. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice.

    PubMed

    Foote, Molly; Arque, Gloria; Berman, Robert F; Santos, Mónica

    2016-10-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.

  4. The evolution of filamin – A protein domain repeat perspective

    PubMed Central

    Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne

    2013-01-01

    Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. PMID:22414427

  5. Cumulative effects from repeated exposures to ultraviolet radiation

    SciTech Connect

    Kaidbey, K.H.; Kligman, A.M.

    1981-05-01

    Repeated exposures to subliminal doses of UVR, given at 24-hr intervals, resulted in a lowering of the erythema threshold dose. At erythemogenically equivalent doses, UV-A was the most effective and UV-C the least. A similar and more pronounced effect was observed following repeated exposures to subthreshold doses of UV-A and topically applied 8-methoxypsoralen. These findings provide quantitative evidence for the cumulative nature of acute UVR damage in human skin.

  6. Repeated nondiagnostic result of thyroid fine-needle aspiration biopsy

    PubMed Central

    Kopczyński, Janusz; Kowalska, Aldona

    2017-01-01

    Aim of the study Fine-needle aspiration biopsy (FNAB) is the most accurate and cost-effective method to evaluate the risk of malignancy of thyroid nodules, but approximately 1–24% of FNABs generate a nondiagnostic result (ND-FNAB). The aim of this study was to determine the predictive factors of a repeated nondiagnostic result of FNAB. Material and methods A total of 4018 FNABs performed in a territorial referral centre were analysed, of which 288 (7.17%) were nondiagnostic. Medical records were available for 245 biopsies performed in 228 patients. The retrospective analysis of factors that may influence a repeat ND-FNAB, including demographic, clinical and ultrasound characteristics, was performed. Results A repeat FNAB was performed in 159 nodules giving a diagnostic result in 79.2% of cases. The time between the biopsies ranged from 1 to 611 days (mean 154.4, median 119). The timing of a repeat FNAB did not significantly alter the diagnostic output (p = 0.29). In the univariate analysis, significant predictors of a repeat ND-FNAB were older patient age (p = 0.02), L-thyroxine supplementation (p = 0.05), and a history of 131I therapy (p < 0.0001). In the multivariate analysis, only a history of 131I therapy was a statistically significant risk factor for a repeat ND-FNAB (p = 0.002). Conclusions Patients with a history of 131I therapy and ND-FNAB should undergo periodic ultrasonographic assessment rather than a repeat biopsy. The interval between repeated FNABs recommended by guidelines does not affect the diagnostic output. PMID:28239289

  7. Optimal entanglement generation for efficient hybrid quantum repeaters

    SciTech Connect

    Azuma, Koji; Sota, Naoya; Yamamoto, Takashi; Koashi, Masato; Imoto, Nobuyuki; Namiki, Ryo; Oezdemir, Sahin Kaya

    2009-12-15

    We propose a realistic protocol to generate entanglement between quantum memories at neighboring nodes in hybrid quantum repeaters. Generated entanglement includes only one type of error, which enables efficient entanglement distillation. In contrast to the known protocols with such a property, our protocol with ideal detectors achieves the theoretical limit of the success probability and the fidelity to a Bell state, promising higher efficiencies in the repeaters. We also show that the advantage of our protocol remains even with realistic threshold detectors.

  8. Quantum repeater based on cavity QED evolutions and coherent light

    NASA Astrophysics Data System (ADS)

    Gonţa, Denis; van Loock, Peter

    2016-05-01

    In the framework of cavity QED, we propose a quantum repeater scheme that uses coherent light and chains of atoms coupled to optical cavities. In contrast to conventional repeater schemes, in our scheme there is no need for an explicit use of two-qubit quantum logical gates by exploiting solely the cavity QED evolution. In our previous work (Gonta and van Loock in Phys Rev A 88:052308, 2013), we already proposed a quantum repeater in which the entanglement between two neighboring repeater nodes was distributed using controlled displacements of input coherent light, while the produced low-fidelity entangled pairs were purified using ancillary (four-partite) entangled states. In the present work, the entanglement distribution is realized using a sequence of controlled phase shifts and displacements of input coherent light. Compared to previous coherent-state-based distribution schemes for two-qubit entanglement, our scheme here relies only upon a simple discrimination of two coherent states with opposite signs, which can be performed in a quantum mechanically optimal fashion via a beam splitter and two on-off detectors. For the entanglement purification, we employ a method that avoids the use of extra entangled ancilla states. Our repeater scheme exhibits reasonable fidelities and repeater rates providing an attractive platform for long-distance quantum communication.

  9. Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway.

    PubMed

    Millership, C; Phillips, J J; Main, E R G

    2016-05-08

    Repeat proteins are formed from units of 20-40 aa that stack together into quasi one-dimensional non-globular structures. This modular repetitive construction means that, unlike globular proteins, a repeat protein's equilibrium folding and thus thermodynamic stability can be analysed using linear Ising models. Typically, homozipper Ising models have been used. These treat the repeat protein as a series of identical interacting subunits (the repeated motifs) that couple together to form the folded protein. However, they cannot describe subunits of differing stabilities. Here we show that a more sophisticated heteropolymer Ising model can be constructed and fitted to two new helix deletion series of consensus tetratricopeptide repeat proteins (CTPRs). This analysis, showing an asymmetric spread of stability between helices within CTPR ensembles, coupled with the Ising model's predictive qualities was then used to guide reprogramming of the unfolding pathway of a variant CTPR protein. The designed behaviour was engineered by introducing destabilising mutations that increased the thermodynamic asymmetry within a CTPR ensemble. The asymmetry caused the terminal α-helix to thermodynamically uncouple from the rest of the protein and preferentially unfold. This produced a specific, highly populated stable intermediate with a putative dimerisation interface. As such it is the first step in designing repeat proteins with function regulated by a conformational switch.

  10. Impact of Repeated Exposures on Information Spreading in Social Networks.

    PubMed

    Zhou, Cangqi; Zhao, Qianchuan; Lu, Wenbo

    2015-01-01

    Clustered structure of social networks provides the chances of repeated exposures to carriers with similar information. It is commonly believed that the impact of repeated exposures on the spreading of information is nontrivial. Does this effect increase the probability that an individual forwards a message in social networks? If so, to what extent does this effect influence people's decisions on whether or not to spread information? Based on a large-scale microblogging data set, which logs the message spreading processes and users' forwarding activities, we conduct a data-driven analysis to explore the answer to the above questions. The results show that an overwhelming majority of message samples are more probable to be forwarded under repeated exposures, compared to those under only a single exposure. For those message samples that cover various topics, we observe a relatively fixed, topic-independent multiplier of the willingness of spreading when repeated exposures occur, regardless of the differences in network structure. We believe that this finding reflects average people's intrinsic psychological gain under repeated stimuli. Hence, it makes sense that the gain is associated with personal response behavior, rather than network structure. Moreover, we find that the gain is robust against the change of message popularity. This finding supports that there exists a relatively fixed gain brought by repeated exposures. Based on the above findings, we propose a parsimonious model to predict the saturated numbers of forwarding activities of messages. Our work could contribute to better understandings of behavioral psychology and social media analytics.

  11. The meaning of sampling density in multiple repeat prostate biopsies

    PubMed Central

    Čapoun, Otakar; Minárik, Ivo; Kýr, Michal; Hanuš, Tomáš; Babjuk, Marek; Sobotka, Roman

    2016-01-01

    Introduction Extended transrectal ultrasound-guided prostate biopsy is a state-of-the-art tool for prostate cancer detection. Nevertheless, approximately 1/3 of cancers are missed when using this method and repeat biopsy sessions are often required. The aim of this study was to investigate how sampling density (a compound variable reflecting the number of biopsy cores and prostate volume) impacts on detection rate in multiple repeat TRUS-biopsies. Material and methods A total of 1007 consecutive patients undergoing their 1st, 2nd, 3rd and any further repeat prostate biopsies were included. The relationship between sampling density and other clinical variables (age, prostate-specific antigen level, free/total PSA ratio, digital rectal examination, number of previous biopsies) and cancer detection rate were assessed by interaction analysis. Results There were 562 primary re-biopsies, 267 second re-biopsies and 178 third and further re-biopsies included in the study. Detection rate was 25.4%, 25.8% and 25.3%, respectively. Interaction of sampling density with age was demonstrated in patients undergoing their first repeat biopsy (but not further re-biopsies). No interaction was observed with other variables investigated. Conclusions A more extensive prostate sampling leads to a higher cancer detection rate on repeat prostate biopsies, as shown previously. However, this effect seems to be particularly pronounced in men younger than 65 years undergoing their first repeat prostate biopsy. PMID:28127449

  12. Considerations on repeated repairing of weldments in Inconel 718 alloy

    NASA Technical Reports Server (NTRS)

    Bayless, E. O.; Lovoy, C. V.; Mcilwain, M. C.; Munafo, P.

    1981-01-01

    The effects of repeated weld repairs on the metallurgical characteristics, high cycle fatigue (HCF), and tensile properties of Inconel 718 butt weld joints were determined. A 1/4 in thick plate and a 1/2 in thick plate were used as well as tungsten inert gas welding, and Inconel 718 filler wire. Weld panels were subjected to 2, 6, and 12 repeated repairs and were made in a highly restrained condition. Post weld heat treatments were also conducted with the welded panel in the highly restrained condition. Results indicate that no significant metallurgical anomaly is evident as a result of up to twelve repeated weld repairs. No degradation in fatigue life is noted for up to twelve repeated repairs. Tensile results from specimens which contained up to twelve repeated weld repairs revealed no significant degradation in UTS and YS. However, a significant decrease in elongation is evident with specimens (solution treated and age hardened after welding) which contained twelve repeated repairs. The elongation loss is attributed to the presence of a severe notch on each side (fusion line) of the repair weld bead reinforcement.

  13. Evolutionary dynamics of satellite DNA repeats from Phaseolus beans.

    PubMed

    Ribeiro, Tiago; Dos Santos, Karla G B; Richard, Manon M S; Sévignac, Mireille; Thareau, Vincent; Geffroy, Valérie; Pedrosa-Harand, Andrea

    2017-03-01

    Common bean (Phaseolus vulgaris) subtelomeres are highly enriched for khipu, the main satellite DNA identified so far in this genome. Here, we comparatively investigate khipu genomic organization in Phaseolus species from different clades. Additionally, we identified and characterized another satellite repeat, named jumper, associated to khipu. A mixture of P. vulgaris khipu clones hybridized in situ confirmed the presence of khipu-like sequences on subterminal chromosome regions in all Phaseolus species, with differences in the number and intensity of signals between species and when species-specific clones were used. Khipu is present as multimers of ∼500 bp and sequence analyses of cloned fragments revealed close relationship among khipu repeats. The new repeat, named jumper, is a 170-bp satellite sequence present in all Phaseolus species and inserted into the nontranscribed spacer (NTS) of the 5S rDNA in the P. vulgaris genome. Nevertheless, jumper was found as a high-copy repeat at subtelomeres and/or pericentromeres in the Phaseolus microcarpus lineage only. Our data argue for khipu as an important subtelomeric satellite DNA in the genus and for a complex satellite repeat composition of P. microcarpus subtelomeres, which also contain jumper. Furthermore, the differential amplification of these repeats in subtelomeres or pericentromeres reinforces the presence of a dynamic satellite DNA library in Phaseolus.

  14. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    SciTech Connect

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  15. Repeated high-intensity exercise in professional rugby union.

    PubMed

    Austin, Damien; Gabbett, Tim; Jenkins, David

    2011-07-01

    The aim of the present study was to describe the frequency, duration, and nature of repeated high-intensity exercise in Super 14 rugby union. Time-motion analysis was used during seven competition matches over the 2008 and 2009 Super 14 seasons; five players from each of four positional groups (front row forwards, back row forwards, inside backs, and outside backs) were assessed (20 players in total). A repeated high-intensity exercise bout was considered to involve three or more sprints, and/or tackles and/or scrum/ruck/maul activities within 21 s during the same passage of play. The range of repeated high-intensity exercise bouts for each group in a match was as follows: 11-18 for front row forwards, 11-21 for back row forwards, 13-18 for inside backs, and 2-11 for outside backs. The durations of the most intense repeated high-intensity exercise bouts for each position ranged from 53 s to 165 s and the minimum recovery periods between repeated high-intensity exercise bouts ranged from 25 s for the back row forwards to 64 s for the front row forwards. The present results show that repeated high-intensity exercise bouts vary in duration and activities relative to position but all players in a game will average at least 10 changes in activity in the most demanding bouts and complete at least one tackle and two sprints. The most intense periods of activity are likely to last as long as 120 s and as little as 25 s recovery may separate consecutive repeated high-intensity exercise bouts. The present findings can be used by coaches to prepare their players for the most demanding passages of play likely to be experienced in elite rugby union.

  16. Tandem repeats of Allium fistulosum associated with major chromosomal landmarks.

    PubMed

    Kirov, Ilya V; Kiseleva, Anna V; Van Laere, Katrijn; Van Roy, Nadine; Khrustaleva, Ludmila I

    2017-04-01

    Tandem repeats are often associated with important chromosomal landmarks, such as centromeres, telomeres, subtelomeric, and other heterochromatic regions, and can be good candidates for molecular cytogenetic markers. Tandem repeats present in many plant species demonstrate dramatic differences in unit length, proportion in the genome, and chromosomal organization. Members of genus Allium with their large genomes represent a challenging task for current genetics. Using the next generation sequencing data, molecular, and cytogenetic methods, we discovered two tandemly organized repeats in the Allium fistulosum genome (2n = 2C = 16), HAT58 and CAT36. Together, these repeats comprise 0.25% of the bunching onion genome with 160,000 copies/1 C of HAT58 and 93,000 copies/1 C of CAT36. Fluorescent in situ hybridization (FISH) and C-banding showed that HAT58 and CAT36 associated with the interstitial and pericentromeric heterochromatin of the A. fistulosum chromosomes 5, 6, 7, and 8. FISH with HAT58 and CAT36 performed on A. cepa (2n = 2C = 16) and A. wakegi (2n = 2C = 16), a natural allodiploid hybrid between A. fistulosum and A. cepa, revealed that these repeats are species specific and produced specific hybridization patterns only on A. fistulosum chromosomes. Thus, the markers can be used in interspecific breeding programs for monitoring of alien genetic material. We applied Non-denaturing FISH that allowed detection of the repeat bearing chromosomes within 3 h. A polymorphism of the HAT58 chromosome location was observed. This finding suggests that the rapid evolution of the HAT58 repeat is still ongoing.

  17. Discrepancy variation of dinucleotide microsatellite repeats in eukaryotic genomes.

    PubMed

    Gao, Huan; Cai, Shengli; Yan, Binlun; Chen, Baiyao; Yu, Fei

    2009-01-01

    To address whether there are differences of variation among repeat motif types and among taxonomic groups, we present here an analysis of variation and correlation of dinucleotide microsatellite repeats in eukaryotic genomes. Ten taxonomic groups were compared, those being primates, mammalia (excluding primates and rodentia), rodentia, birds, fish, amphibians and reptiles, insects, molluscs, plants and fungi, respectively. The data used in the analysis is from the literature published in the Journal of Molecular Ecology Notes. Analysis of variation reveals that there are no significant differences between AC and AG repeat motif types. Moreover, the number of alleles correlates positively with the copy number in both AG and AC repeats. Similar conclusions can be obtained from each taxonomic group. These results strongly suggest that the increase of SSR variation is almost linear with the increase of the copy number of each repeat motif. As well, the results suggest that the variability of SSR in the genomes of low-ranking species seem to be more than that of high-ranking species, excluding primates and fungi.

  18. Design and analysis of communication protocols for quantum repeater networks

    NASA Astrophysics Data System (ADS)

    Jones, Cody; Kim, Danny; Rakher, Matthew T.; Kwiat, Paul G.; Ladd, Thaddeus D.

    2016-08-01

    We analyze how the performance of a quantum-repeater network depends on the protocol employed to distribute entanglement, and we find that the choice of repeater-to-repeater link protocol has a profound impact on entanglement-distribution rate as a function of hardware parameters. We develop numerical simulations of quantum networks using different protocols, where the repeater hardware is modeled in terms of key performance parameters, such as photon generation rate and collection efficiency. These parameters are motivated by recent experimental demonstrations in quantum dots, trapped ions, and nitrogen-vacancy centers in diamond. We find that a quantum-dot repeater with the newest protocol (‘MidpointSource’) delivers the highest entanglement-distribution rate for typical cases where there is low probability of establishing entanglement per transmission, and in some cases the rate is orders of magnitude higher than other schemes. Our simulation tools can be used to evaluate communication protocols as part of designing a large-scale quantum network.

  19. Alanine repeats influence protein localization in splicing speckles and paraspeckles.

    PubMed

    Chang, Shuo-Hsiu; Chang, Wei-Lun; Lu, Chia-Chen; Tarn, Woan-Yuh

    2014-12-16

    Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated-fully or partially-from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ.

  20. Repeat expansion and autosomal dominant neurodegenerative disorders: consensus and controversy.

    PubMed

    Rudnicki, Dobrila D; Margolis, Russell L

    2003-08-22

    Repeat-expansion mutations cause 13 autosomal dominant neurodegenerative disorders falling into three groups. Huntington's disease (HD), dentatorubral pallidoluysian atrophy (DRPLA), spinal and bulbar muscular atrophy (SBMA), and spinocerebellar ataxias (SCAs) types 1, 2, 3, 7 and 17 are each caused by a CAG repeat expansion that encodes polyglutamine. Convergent lines of evidence demonstrate that neurodegeneration in these diseases is a consequence of the neurotoxic effects of abnormally long stretches of glutamines. How polyglutamine induces neurodegeneration, and why neurodegeneration occurs in only select neuronal populations, remains a matter of intense investigation. SCA6 is caused by a CAG repeat expansion in CACNA1A, a gene that encodes a subunit of the P/Q-type calcium channel. The threshold length at which the repeat causes disease is much shorter than in the other polyglutamine diseases, and neurodegeneration may arise from expansion-induced change of function in the calcium channel. Huntington's disease-like 2 (HDL2) and SCAs 8, 10 and 12 are rare disorders in which the repeats (CAG, CTG or ATTCT) are not in protein-coding regions. Investigation into these diseases is still at an early stage, but it is now reasonable to hypothesise that the net effect of each expansion is to alter gene expression. The different pathogenic mechanisms in these three groups of diseases have important implications for the development of rational therapeutics.

  1. Polymorphism of CAG repeats in androgen receptor of carnivores.

    PubMed

    Wang, Qin; Zhang, Xiuyue; Wang, Xiaofang; Zeng, Bo; Jia, Xiaodong; Hou, Rong; Yue, Bisong

    2012-03-01

    Androgen effect is mediated by the androgen receptor (AR). The polymorphism of CAG triplet repeat (polyCAG), in the N-terminal transactivation domain of the AR protein, has been involved either in endocrine or neurological disorders in human. We obtained partial sequence of AR exon 1 in 10 carnivore species. In most carnivore species, polyglutamine length polymorphism presented in all three CAG repeat regions of AR, in contrast, only CAG-I site polymorphism presented in primate species, and CAG-I and CAG-III sites polymorphism presented in Canidae. Therefore, studies focusing on disease-associated polymorphism of poly(CAG) in carnivore species AR should investigate all three CAG repeats sites, and should not only consider CAG-I sites as the human disease studies. The trinucleotide repeat length in carnivore AR exon 1 had undergone from expansions to contractions during carnivores evolution, unlike a linear increase in primate species. Furthermore, the polymorphisms of the triplet-repeats in the same tissue (somatic mosaicism) were demonstrated in Moutain weasel, Eurasian lynx, Clouded leopard, Chinese tiger, Black leopard and Leopard AR. And, the abnormal stop codon was found in the exon 1 of three carnivore species AR (Moutain weasel, Eurasian lynx and Black leopard). It seemed to have a high frequency presence of tissue-specific somatic in carnivores AR genes. Thus the in vivo mechanism leading to such highly variable phenotypes of the described mutations, and their impact on these animals, are worthwhile to be further elucidated.

  2. Computer Simulation Studies of CTG Triplet Repeat Sequences

    NASA Astrophysics Data System (ADS)

    Rasaiah, Jayendran. C.; Lynch, Joshua

    1998-03-01

    Long segments of CTG trinucleotide repeats in human DNA are correlated with a class of neurological diseases (myotonic dystrophy, fragile-X syndrome, and Kenndy's disease). These diseases are characterized by genetic anticipation and are thought to arise from replication errors caused by unusual conformations of CTG repeat segments. We have studied the properties of a single short segment of double starnded DNA with CTG repeats in 0.5 M sodium chloride solution with molecular dynamics simulations. The simulations are carried out in the micro canonical ensemble using an all-atom force field with CHARMM parameters. The TIPS3 water model is used to simulate a molecular solvent. Electrostatic interactions are calculated by Ewald summation and the equations of motion integrated using a Verlet algorithm in conjunction with SHAKE constrained dynamics to maintain bond lengths. The simulation of CTG repeat sequence is compared with a control system containing CAG triplet repeats to determine possible differencesin the conformation and elasticity of the two sequences.

  3. Repeat instability during DNA repair: Insights from model systems

    PubMed Central

    Usdin, Karen; House, Nealia C. M.; Freudenreich, Catherine H.

    2015-01-01

    The expansion of repeated sequences is the cause of over 30 inherited genetic diseases, including Huntington disease, myotonic dystrophy (types 1 and 2), fragile X syndrome, many spinocerebellar ataxias, and some cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat expansions are dynamic, and disease inheritance and progression are influenced by the size and the rate of expansion. Thus, an understanding of the various cellular mechanisms that cooperate to control or promote repeat expansions is of interest to human health. In addition, the study of repeat expansion and contraction mechanisms has provided insight into how repair pathways operate in the context of structure-forming DNA, as well as insights into non-canonical roles for repair proteins. Here we review the mechanisms of repeat instability, with a special emphasis on the knowledge gained from the various model systems that have been developed to study this topic. We cover the repair pathways and proteins that operate to maintain genome stability, or in some cases cause instability, and the cross-talk and interactions between them. PMID:25608779

  4. Implementation of bipartite or remote unitary gates with repeater nodes

    NASA Astrophysics Data System (ADS)

    Yu, Li; Nemoto, Kae

    2016-08-01

    We propose some protocols to implement various classes of bipartite unitary operations on two remote parties with the help of repeater nodes in-between. We also present a protocol to implement a single-qubit unitary with parameters determined by a remote party with the help of up to three repeater nodes. It is assumed that the neighboring nodes are connected by noisy photonic channels, and the local gates can be performed quite accurately, while the decoherence of memories is significant. A unitary is often a part of a larger computation or communication task in a quantum network, and to reduce the amount of decoherence in other systems of the network, we focus on the goal of saving the total time for implementing a unitary including the time for entanglement preparation. We review some previously studied protocols that implement bipartite unitaries using local operations and classical communication and prior shared entanglement, and apply them to the situation with repeater nodes without prior entanglement. We find that the protocols using piecewise entanglement between neighboring nodes often require less total time compared to preparing entanglement between the two end nodes first and then performing the previously known protocols. For a generic bipartite unitary, as the number of repeater nodes increases, the total time could approach the time cost for direct signal transfer from one end node to the other. We also prove some lower bounds of the total time when there are a small number of repeater nodes. The application to position-based cryptography is discussed.

  5. Elective repeat cesarean sections: how many could be vaginal births?

    PubMed Central

    Norman, P; Kostovcik, S; Lanning, A

    1993-01-01

    OBJECTIVE: To determine (a) the proportion of women undergoing elective repeat cesarean section without a trial of labour who were eligible for such a trial by the 1986 guidelines of the panel of the National Consensus Conference on Aspects of Cesarean Birth, (b) whether vaginal birth after cesarean section (VBAC) was discussed with these women and (c) the reasons cited for not having a trial of labour. DESIGN: Chart audit. SETTING: Level 2 perinatal care centre in a general teaching hospital. PATIENTS: All 313 women with a history of previous cesarean section who gave birth at the centre during 1989. RESULTS: Only 93 (30%) of the 313 women underwent a trial of labour. According to the 1986 guidelines 71% were eligible. A further 13% would have been eligible according to the revised 1991 guidelines. Of the 220 women who underwent elective repeat cesarean section, only 24 (11%) had a discussion of VBAC noted in their hospital charts. However, of all 117 patients whose charts indicated discussion of VBAC 93 (79%) chose to try it. Most of the women had either questionable indications or no indication noted for undergoing repeat cesarean section. CONCLUSION: Most of the women who underwent repeat cesarean section were eligible for a trial of labour. However, few charts noted a discussion of VBAC. Further physician and patient education is necessary to promote the appropriate use of VBAC and repeat cesarean section. PMID:8348425

  6. Diagnosis of repeated failures in discrete event systems.

    SciTech Connect

    Garcia, H. E.; Jiang, S.; Kumar, R.; Univ. of Kentucky; Iowa State Univ.

    2002-01-01

    We introduce the notion of repeated failure diagnosability for diagnosing the occurrence of a repeated number of failures in discrete event systems. This generalizes the earlier notion of diagnosability that was used to diagnose the occurrence of a failure, but from which the information regarding the multiplicity of the occurrence of the failure could not be obtained. It is possible that in some systems the same type of failure repeats a multiple number of times. It is desirable to have a diagnoser which not only diagnoses that such a failure has occurred but also determines the number of times the failure has occurred. To aide such analysis we introduce the notions of K-diagnosability (K failures diagnosability), [1, K]-diagnosability (1 through K failures diagnosability), and [1, /spl infin/]-diagnosability (1 through /spl infin/ failures diagnosability). Here the first notion is the weakest of all three, and the earlier notion of diagnosability is the same as that of K-diagnosability or that of [1, K]-diagnosability with K=1. We give polynomial algorithms for checking these various notions of repeated failure diagnosability, and also present a procedure of polynomial complexity for the online diagnosis of repeated failures.

  7. Diagnosis of repeated/intermittent failures in discrete event systems.

    SciTech Connect

    Garcia, H. E.; Jiang, S.; Kumar, R.

    2003-04-01

    We introduce the notion of repeated failure diagnosability for diagnosing the occurrence of a repeated number of failures in discrete event systems. This generalizes the earlier notion of diagnosability that was used to diagnose the occurrence of a failure, but from which the information regarding the multiplicity of the occurrence of the failure could not be obtained. It is possible that in some systems the same type of failure repeats a multiple number of times. It is desirable to have a diagnoser which not only diagnoses that such a failure has occurred but also determines the number of times the failure has occurred. To aide such analysis we introduce the notions of K-diagnosability (K failures diagnosability), [1,K]-diagnosability (1 through K failures diagnosability), and [1,1]-diagnosability (1 through 1 failures diagnosability). Here the rst (resp., last) notion is the weakest (resp., strongest) of all three, and the earlier notion of diagnosability is the same as that of K-diagnosability or that of [1,K]- diagnosability with K = 1. We give polynomial algorithms for checking these various notions of repeated failure diagnosability, and also present a procedure of polynomial complexity for the on-line diagnosis of repeated failures.

  8. Analysing two dinucleotide repeats of FVIII gene in Iranian population.

    PubMed

    Rabbani, B; Rezaeian, A; Khanahmad, H; Bagheri, R; Kamali, E; Zeinali, S

    2007-11-01

    Using dinucleotide repeats for carrier detection and prenatal diagnosis of haemophilia A patients, led us to find different alleles and their frequencies in Iranian population. Polymerase chain reaction (PCR) amplification of two short tandem repeat (STR) loci of factor VIII (FVIII) gene was performed, and the PCR products were resolved on 10% native polyacrylamide gel, and samples were analysed with sequenced DNA markers made of PCR cloning of the dinucleotide FVIII gene fragments. Seven different alleles were observed for intron 13 STR, having 18-24 (CA) repeating units and five alleles for intron 22 STR having 24-28 repeating units of (CACT). Bands produced during dinucleotide study were defined in detail so this could improve the genotyping of heterozygotes and homozygotes. Conformational band produced were characterized to specify the dinucleotide pattern. Our results confirm the Hardy-Weinberg proportions of the heterozygosity rate of the 85 analysed individuals. The observed heterozygosity rate for intron 13 and 22 was 52% and 59% respectively. Our data also indicate that our population is closer to caucasians than to any other populations. Finding different dinucleotide repeat alleles and their frequencies has made it possible to identify carriers and provide prenatal diagnosis with more confidence. This allows antenatal diagnosis to be performed in the vast majority of carriers.

  9. FMR1 in global populations

    SciTech Connect

    Kunst, C.B.; Zerylnick, C.; Karickhoff, L.

    1996-03-01

    Fragile X syndrome, a frequent form of inherited mental retardation, results from the unstable expansion of a cryptic CGG repeat within the 5{prime} UTR region of the FMR1 gene. The CGG repeat is normally polymorphic in length, and the content is frequently interrupted by AGG triplets. These interruptions are believed to stabilize the repeat, and their absence, leading to long tracts of perfect CGG repeats, may give rise to predisposed alleles. In order to examine the stability of normal FMR1 alleles, the repeat length of 345 chromosomes from nine global populations was examined with the content also determined from 114 chromosomes as assessed by automated DNA sequencing. The FMR1 alleles, defined by the CGG repeat, as well as by the haplotypes of nearby polymorphic loci, were very heterogeneous, although the level of variation correlated with the age and/or genetic history of a particular population. Native American alleles, interrupted by three AGG repeats, exhibited marked stability over 7,000 years. However, in older African populations, parsimony analysis predicts the occasional loss of an AGG, leading to more perfect CGG repeats. These data therefore support the suggestion that AGG interruptions enhance the stability of the FMR1 repeat and indicate that the rare loss of these interruptions leads to alleles with longer perfect CGG-repeat tracts. 42 refs., 4 figs., 2 tabs.

  10. Chronic adhesive arachnoiditis after repeat epidural blood patch.

    PubMed

    Carlswärd, C; Darvish, B; Tunelli, J; Irestedt, L

    2015-08-01

    Epidural blood patching is an effective treatment for postdural puncture headache but has potential risks. Arachnoiditis is a very rare disabling condition and few cases have been described following an epidural blood patch. We present a case of chronic adhesive arachnoiditis in a parturient treated with a repeat epidural blood patch. A healthy 29-year-old woman had an accidental dural puncture following epidural insertion during labour. Initial treatment of postdural puncture headache with an epidural blood patch was ineffective and was therefore repeated. She gradually developed severe neurological symptoms consistent with arachnoiditis confirmed with magnetic resonance imaging. Despite intensive multimodal treatment with analgesics and physiotherapy, her neurological condition remains unresolved two years later. This serious but rare complication should encourage caution when treating parturients with postdural puncture headache with a repeat epidural blood patch.

  11. A PLL Synthesizer with Learning Repeatable Fluctuation of Input Signal

    NASA Astrophysics Data System (ADS)

    Ono, Hiroyuki

    This paper describes a high frequency PLL (Phase Locked Loop) synthesizer with a function of learning then eliminating repeatable fluctuation of timing intervals on series input pulses. Typical spindle encoder generates digital pulses according to the revolution speed. The intervals of each pulse have repeatable fluctuation every revolution by eccentricity or warpage of the encoder scale disk. This method provides a programmable counter for the loop counter of PLL circuit and an interval counter with memory in order to learn the repeatable fluctuation. After the learning process, the PLL generates very pure tone clock signal based on the real flutter components of the spindle revolution speed without influenced by encoder errors. This method has been applied to a hard disk test system in order to generate 3GHz read/write clock.

  12. Archery performance level and repeatability of event-related EMG.

    PubMed

    Soylu, A R; Ertan, H; Korkusuz, F

    2006-12-01

    The purpose of the current study was to compare the repeatability of electromyographic linear envelopes (LE) of archery groups. Surface electromyography (EMG) signals of musculus flexor digitorum superficialis (MFDS) and extensor digitorum (MED) of 23 participants (seven skilled, six beginner archers and ten non-archers) were recorded during archery shooting. Two-second periods (clicker falls at first second) of 12 shots' EMG data were recorded, full-wave rectified and filtered (60 ms moving-average filter) for each participant's drawing arm. Repeatability was investigated by using a statistical criterion, variance ratio (VR). Archers' performances were evaluated in terms of FITA scores. The results showed that FITA scores were significantly correlated to the VRs of MFDS and MED. EMG LEs were more repeatable among archers than non-archers. Therefore, we inferred that VRs of MFDS and MED might be important variables for (a) assessing shooting techniques, (b) evaluation of archers' progress, and (c) selection of talented archers.

  13. Repeat expansion disease: Progress and puzzles in disease pathogenesis

    PubMed Central

    La Spada, Albert R.; Taylor, J. Paul

    2015-01-01

    Repeat expansion mutations cause at least 22 inherited neurological diseases. The complexity of repeat disease genetics and pathobiology has revealed unexpected shared themes and mechanistic pathways among the diseases, for example, RNA toxicity. Also, investigation of the polyglutamine diseases has identified post-translational modification as a key step in the pathogenic cascade, and has shown that the autophagy pathway plays an important role in the degradation of misfolded proteins – two themes likely to be relevant to the entire neurodegeneration field. Insights from repeat disease research are catalyzing new lines of study that should not only elucidate molecular mechanisms of disease, but also highlight opportunities for therapeutic intervention for these currently untreatable disorders. PMID:20177426

  14. Precise estimation of repeating earthquake moment: Example from parkfield, california

    USGS Publications Warehouse

    Rubinstein, J.L.; Ellsworth, W.L.

    2010-01-01

    We offer a new method for estimating the relative size of repeating earthquakes using the singular value decomposition (SVD). This method takes advantage of the highly coherent waveforms of repeating earthquakes and arrives at far more precise and accurate descriptions of earthquake size than standard catalog techniques allow. We demonstrate that uncertainty in relative moment estimates is reduced from ??75% for standard coda-duration techniques employed by the network to an uncertainty of ??6.6% when the SVD method is used. This implies that a single-station estimate of moment using the SVD method has far less uncertainty than the whole-network estimates of moment based on coda duration. The SVD method offers a significant improvement in our ability to describe the size of repeating earthquakes and thus an opportunity to better understand how they accommodate slip as a function of time.

  15. Structural analysis of a multifunctional, tandemly repeated inositol polyphosphatase.

    PubMed

    Gruninger, Robert J; Selinger, L Brent; Mosimann, Steven C

    2009-09-11

    Mitsuokella multacida expresses a unique inositol polyphosphatase (PhyAmm) that is composed of tandem repeats (TRs). Each repeat possesses a protein tyrosine phosphatase (PTP) active-site signature sequence and fold. Using a combination of structural, mutational, and kinetic studies, we show that the N-terminal (D1) and C-terminal (D2) active sites of the TR have diverged and possess significantly different specificities for inositol polyphosphate. Structural analysis and molecular docking calculations identify steric and electrostatic differences within the substrate binding pocket of each TR that may be involved in the altered substrate specificity. The implications of our results for the biological function of related PTP-like phytases are discussed. Finally, the structures and activities of PhyAmm and tandemly repeated receptor PTPs are compared and discussed. To our knowledge, this is the first example of an inositol phosphatase with tandem PTP domains possessing substrate specificity for different inositol phosphates.

  16. Tandem repeat distribution of gene transcripts in three plant families

    PubMed Central

    2009-01-01

    Tandem repeats (microsatellites or SSRs) are molecular markers with great potential for plant genetic studies. Modern strategies include the transfer of these markers among widely studied and orphan species. In silico analyses allow for studying distribution patterns of microsatellites and predicting which motifs would be more amenable to interspecies transfer. Transcribed sequences (Unigene) from ten species of three plant families were surveyed for the occurrence of micro and minisatellites. Transcripts from different species displayed different rates of tandem repeat occurrence, ranging from 1.47% to 11.28%. Both similar and different patterns were found within and among plant families. The results also indicate a lack of association between genome size and tandem repeat fractions in expressed regions. The conservation of motifs among species and its implication on genome evolution and dynamics are discussed. PMID:21637460

  17. Nonlinear analysis of correlations in Alu repeat sequences in DNA

    NASA Astrophysics Data System (ADS)

    Xiao, Yi; Huang, Yanzhao; Li, Mingfeng; Xu, Ruizhen; Xiao, Saifeng

    2003-12-01

    We report on a nonlinear analysis of deterministic structures in Alu repeats, one of the richest repetitive DNA sequences in the human genome. Alu repeats contain the recognition sites for the restriction endonuclease AluI, which is what gives them their name. Using the nonlinear prediction method developed in chaos theory, we find that all Alu repeats have novel deterministic structures and show strong nonlinear correlations that are absent from exon and intron sequences. Furthermore, the deterministic structures of Alus of younger subfamilies show panlike shapes. As young Alus can be seen as mutation free copies from the “master genes,” it may be suggested that the deterministic structures of the older subfamilies are results of an evolution from a “panlike” structure to a more diffuse correlation pattern due to mutation.

  18. Impact of Repeated Exposures on Information Spreading in Social Networks

    PubMed Central

    Zhou, Cangqi; Zhao, Qianchuan; Lu, Wenbo

    2015-01-01

    Clustered structure of social networks provides the chances of repeated exposures to carriers with similar information. It is commonly believed that the impact of repeated exposures on the spreading of information is nontrivial. Does this effect increase the probability that an individual forwards a message in social networks? If so, to what extent does this effect influence people’s decisions on whether or not to spread information? Based on a large-scale microblogging data set, which logs the message spreading processes and users’ forwarding activities, we conduct a data-driven analysis to explore the answer to the above questions. The results show that an overwhelming majority of message samples are more probable to be forwarded under repeated exposures, compared to those under only a single exposure. For those message samples that cover various topics, we observe a relatively fixed, topic-independent multiplier of the willingness of spreading when repeated exposures occur, regardless of the differences in network structure. We believe that this finding reflects average people’s intrinsic psychological gain under repeated stimuli. Hence, it makes sense that the gain is associated with personal response behavior, rather than network structure. Moreover, we find that the gain is robust against the change of message popularity. This finding supports that there exists a relatively fixed gain brought by repeated exposures. Based on the above findings, we propose a parsimonious model to predict the saturated numbers of forwarding activities of messages. Our work could contribute to better understandings of behavioral psychology and social media analytics. PMID:26465749

  19. Repeatability of locomotor performance and morphology-locomotor performance relationships.

    PubMed

    Conradsen, Cara; Walker, Jeffrey A; Perna, Catherine; McGuigan, Katrina

    2016-09-15

    There is good evidence that natural selection drives the evolution of locomotor performance, but the processes that generate the among-individual variation for selection to act on are relatively poorly understood. We measured prolonged swimming performance, Ucrit, and morphology in a large cohort (n=461) of wild-type zebrafish (Danio rerio) at ∼6 months and again at ∼9 months. Using mixed-model analyses to estimate repeatability as the intraclass correlation coefficient, we determined that Ucrit was significantly repeatable (r=0.55; 95% CI: 0.45-0.64). Performance differences between the sexes (males 12% faster than females) and changes with age (decreasing 0.07% per day) both contributed to variation in Ucrit and, therefore, the repeatability estimate. Accounting for mean differences between sexes within the model decreased the estimate of Ucrit repeatability to 21% below the naïve estimate, while fitting age in the models increased the estimate to 14% above the naïve estimate. Greater consideration of factors such as age and sex is therefore necessary for the interpretation of performance repeatability in wild populations. Body shape significantly predicted Ucrit in both sexes in both assays, with the morphology-performance relationship significantly repeatable at the population level. However, morphology was more strongly predicative of performance in older fish, suggesting a change in the contribution of morphology relative to other factors such as physiology and behaviour. The morphology-performance relationship changed with age to a greater extent in males than females.

  20. Rate-loss analysis of an efficient quantum repeater architecture

    NASA Astrophysics Data System (ADS)

    Guha, Saikat; Krovi, Hari; Fuchs, Christopher A.; Dutton, Zachary; Slater, Joshua A.; Simon, Christoph; Tittel, Wolfgang

    2015-08-01

    We analyze an entanglement-based quantum key distribution (QKD) architecture that uses a linear chain of quantum repeaters employing photon-pair sources, spectral-multiplexing, linear-optic Bell-state measurements, multimode quantum memories, and classical-only error correction. Assuming perfect sources, we find an exact expression for the secret-key rate, and an analytical description of how errors propagate through the repeater chain, as a function of various loss-and-noise parameters of the devices. We show via an explicit analytical calculation, which separately addresses the effects of the principle nonidealities, that this scheme achieves a secret-key rate that surpasses the Takeoka-Guha-Wilde bound—a recently found fundamental limit to the rate-vs-loss scaling achievable by any QKD protocol over a direct optical link—thereby providing one of the first rigorous proofs of the efficacy of a repeater protocol. We explicitly calculate the end-to-end shared noisy quantum state generated by the repeater chain, which could be useful for analyzing the performance of other non-QKD quantum protocols that require establishing long-distance entanglement. We evaluate that shared state's fidelity and the achievable entanglement-distillation rate, as a function of the number of repeater nodes, total range, and various loss-and-noise parameters of the system. We extend our theoretical analysis to encompass sources with nonzero two-pair-emission probability, using an efficient exact numerical evaluation of the quantum state propagation and measurements. We expect our results to spur formal rate-loss analysis of other repeater protocols and also to provide useful abstractions to seed analyses of quantum networks of complex topologies.

  1. GTAG- and CGTC-tagged palindromic DNA repeats in prokaryotes

    PubMed Central

    2013-01-01

    Background REPs (Repetitive Extragenic Palindromes) are small (20–40 bp) palindromic repeats found in high copies in some prokaryotic genomes, hypothesized to play a role in DNA supercoiling, transcription termination, mRNA stabilization. Results We have monitored a large number of REP elements in prokaryotic genomes, and found that most can be sorted into two large DNA super-families, as they feature at one end unpaired motifs fitting either the GTAG or the CGTC consensus. Tagged REPs have been identified in >80 species in 8 different phyla. GTAG and CGTC repeats reside predominantly in microorganisms of the gamma and alpha division of Proteobacteria, respectively. However, the identification of members of both super- families in deeper branching phyla such Cyanobacteria and Planctomycetes supports the notion that REPs are old components of the bacterial chromosome. On the basis of sequence content and overall structure, GTAG and CGTC repeats have been assigned to 24 and 4 families, respectively. Of these, some are species-specific, others reside in multiple species, and several organisms contain different REP types. In many families, most units are close to each other in opposite orientation, and may potentially fold into larger secondary structures. In different REP-rich genomes the repeats are predominantly located between unidirectionally and convergently transcribed ORFs. REPs are predominantly located downstream from coding regions, and many are plausibly transcribed and function as RNA elements. REPs located inside genes have been identified in several species. Many lie within replication and global genome repair genes. It has been hypothesized that GTAG REPs are miniature transposons mobilized by specific transposases known as RAYTs (REP associated tyrosine transposases). RAYT genes are flanked either by GTAG repeats or by long terminal inverted repeats (TIRs) unrelated to GTAG repeats. Moderately abundant families of TIRs have been identified in

  2. Two random repeat recall methods to assess alcohol use.

    PubMed Central

    Midanik, L T

    1993-01-01

    Two random repeat recall methods were compared with a summary measure to assess alcohol use. Subjects (n = 142) were randomly assigned to one of two groups; they were called either on 14 random days during three 30-day waves and asked about drinking yesterday, or on 2 random days during each wave and asked about drinking in the past week. Follow-up telephone interviews obtained summary measures for each wave. Random repeat methods generally obtained higher estimates. However, the high dropout rate makes questionable the feasibility of using this approach with general population samples. PMID:8498631

  3. The Repeat Expansion Diseases: the dark side of DNA repair?

    PubMed Central

    Zhao, Xiao-Nan; Usdin, Karen

    2015-01-01

    DNA repair normally protects the genome against mutations that threaten genome integrity and thus cell viability. However, growing evidence suggests that in the case of the Repeat Expansion Diseases, disorders that result from an increase in the size of a disease-specific microsatellite, the disease-causing mutation is actually the result of aberrant DNA repair. A variety of proteins from different DNA repair pathways have thus far been implicated in this process. This review will summarize recent findings from patients and from mouse models of these diseases that shed light on how these pathways may interact to cause repeat expansion. PMID:26002199

  4. Repeated recall and PKMζ maintain fear memories in juvenile rats.

    PubMed

    Oliver, Chicora F; Kabitzke, Patricia; Serrano, Peter; Egan, Laura J; Barr, Gordon A; Shair, Harry N; Wiedenmayer, Christoph

    2016-12-01

    We examined the neural substrates of fear memory formation and maintenance when repeated recall was used to prevent forgetting in young animals. In contrast to adult rats, juveniles failed to show contextual fear responses at 4 d post-fear conditioning. Reconsolidation sessions 3 and 6 d after conditioning restored contextual fear responses in juveniles 7 d after initial training. In juveniles that received reconsolidation sessions, protein kinase M zeta (PKMζ) increased in the amygdala, but not in the hippocampus. These data suggest that repeated reminders and increased PKMζ maintain fear responses in juvenile animals that otherwise would not exhibit this behavior.

  5. A selective-repeat ARQ scheme and its throughput analysis

    NASA Astrophysics Data System (ADS)

    Chitre, D. M.

    A selective-repeat ARQ (automatic repeat request) scheme that uses a finite receiver buffer is investigated. A Markov process is identified which describes the proposed ARQ scheme with a receiver buffer of size N. It leads to an irreducible, aperiodic, finite, and stationary Markov chain. The resulting stationary probability distribution is then used to compute exactly the throughput efficiency. Analytical results show that the proposed protocol significantly outperforms the go-back-N ARQ protocol and its variations over a wide range of channel capacities and bit error rates.

  6. Contraction of fully expanded FMR1 alleles to the normal range: predisposing haplotype or rare events?

    PubMed

    Maia, Nuno; Loureiro, Joana R; Oliveira, Bárbara; Marques, Isabel; Santos, Rosário; Jorge, Paula; Martins, Sandra

    2017-02-01

    Fragile X syndrome (FXS), the most common cause of inherited intellectual disability, is due to the expansion over 200 CGGs and methylation of this polymorphic region, in the 5'-UTR (untranslated region) of FMR1 (Xq27.3). We have identified four FXS mosaic males: M1-(CGG)35/(CGG)>200; M2-(CGG)26/(CGG)>200; M3-(CGG)39/(CGG)>200; and M4-(CGG)18/(CGG)125/(CGG)>200. After genotyping their respective mothers, we suggested that normal alleles of these patients resulted from post-zygotic contractions of full expansions. The detection of these four rare independent cases led us to hypothesize the existence of a large-contraction predisposing haplotype in our population. Next, we questioned whether other normal pure CGGs would have arisen through similar contractions from fully expanded alleles. To address these questions, we identified stable single-nucleotide polymorphism (SNP) lineages and related short tandem repeat (STR) haplotypes (DXS998-DXS548-FRAXAC1-FRAXAC2) of the four mosaics, 123 unrelated FXS patients and 212 controls. An extended flanking haplotype (34-44-38-336) shared by mosaics from lineage A suggested a risk lineage-specific haplotype more prone to large contractions. Other normal pure FMR1 alleles from this SNP background also shared phylogenetically close STR haplotypes, although a single (CGG)exp>(CGG)24 contraction or the loss of AGG interruptions may explain their origin. In both scenarios, multistep FMR1 mutations involving the gain or loss of several CGGs seem to underlie the evolution of the repeat.

  7. Isolation and characterization of recombinant DNAs containing repeated elements of barley genome: identification of individual actively transcribed families of repeats

    SciTech Connect

    Prosnyak, M.I.; Kartel', N.A.; Ryskov, A.P.

    1986-05-01

    A bank of Escherichia coli clones containing fragments of barley nuclear DNA was obtained using plasmid pBR 322. Clones carrying repeated sequences of the plant genome were selected by means of colony and blot hybridization. Clones with actively transcribed sequences were selected by hybridization to complementary DNA synthesized by means of reverse transcription on a template of total barley poly(A)-containing RNA. Individual families of repeats, two of which contained transcriptionally active sequences of the barley genome, were identified by blot hybridization of recombinant plasmids containing labeled DNA fragments of the inserts of three different clones.

  8. Repeatedly Reactivated Memories Become More Resistant to Hippocampal Damage

    ERIC Educational Resources Information Center

    Lehmann, Hugo; McNamara, Kathryn C.

    2011-01-01

    We examined whether repeated reactivations of a context memory would prevent the typical amnesic effects of post-training damage to the hippocampus (HPC). Rats were given a single contextual fear-conditioning session followed by 10 reactivations, involving a brief return to the conditioning context (no shock). Subsequently, the rats received sham…

  9. Cis-elements governing trinucleotide repeat instability in Saccharomyces cerevisiae.

    PubMed Central

    Rolfsmeier, M L; Dixon, M J; Pessoa-Brandão, L; Pelletier, R; Miret, J J; Lahue, R S

    2001-01-01

    Trinucleotide repeat (TNR) instability in humans is governed by unique cis-elements. One element is a threshold, or minimal repeat length, conferring frequent mutations. Since thresholds have not been directly demonstrated in model systems, their molecular nature remains uncertain. Another element is sequence specificity. Unstable TNR sequences are almost always CNG, whose hairpin-forming ability is thought to promote instability by inhibiting DNA repair. To understand these cis-elements further, TNR expansions and contractions were monitored by yeast genetic assays. A threshold of approximately 15--17 repeats was observed for CTG expansions and contractions, indicating that thresholds function in organisms besides humans. Mutants lacking the flap endonuclease Rad27p showed little change in the expansion threshold, suggesting that this element is not altered by the presence or absence of flap processing. CNG or GNC sequences yielded frequent mutations, whereas A-T rich sequences were substantially more stable. This sequence analysis further supports a hairpin-mediated mechanism of TNR instability. Expansions and contractions occurred at comparable rates for CTG tract lengths between 15 and 25 repeats, indicating that expansions can comprise a significant fraction of mutations in yeast. These results indicate that several unique cis-elements of human TNR instability are functional in yeast. PMID:11290713

  10. Comparative Analysis of Alu Repeats in Primate Genomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Alu repeats are SINEs (Short intersperse repetitive elements) which enjoy a successful application in genome evolution, population biology, phylogenetics and forensics. Human Alu consensus sequences were widely used as surrogates in nonhuman primate studies with an assumption that all p...

  11. 47 CFR 90.247 - Mobile repeater stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... repeater to extend the communications range of hand-carried units subject to the following: (a) Mobile... same frequency is also used by the same station for direct communication with vehicular mobile units or... of the mobile unit and an automatic time-delay device that de-activates the transmitter after...

  12. Physiological responses to repeated transportation of gestating Brahman cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The transportation process acts as a stressor with adverse effects on animal health and performance. The purpose of this study was to examine physiological responses to repeated transportation of gestating Brahman cows, previously classified as mature cows, into temperament groups of calm, moderate,...

  13. Central effects following repeated treatment with antidepressant drugs.

    PubMed

    Maj, J

    1984-01-01

    The review sums up the results of experiments in which there were studied central effects following repeated administration of various antidepressant drugs (AD) in rats and mice. A number of typical and atypical AD, except for selective inhibitors of 5-hydroxytryptamine (5-HT) uptake, potentiate the clonidine aggressiveness in mice (medicated by alpha 1-adrenoceptors). These results indicate that the repeated AD administration enhances responsiveness of central postsynaptic alpha 1-adrenoceptors. This assumption is in accordance with electrophysiological literature data. A few AD (including citalopram, a selective inhibitor of the 5-HT uptake), administered repeatedly, potentiate the locomotor hyperactivity induced by D-amphetamine or apomorphine, without affecting the stereotypy evoked by both dopaminomimetics. It may be supposed that AD enhance the responsiveness of a dopamine (DA) system, probably the mesolimbic one (but not the striatal one). A repeated administration of various AD also counteracts the locomotor hypoactivity induced by salbutamol (mediated by a beta-adrenoceptor). The importance of the effects stated above (alpha 1 up-regulation, DA up-regulation, beta down-regulation) for the mechanism of antidepressant action has been discussed.

  14. Identifying repeat DUI crash factors using state crash records.

    PubMed

    Fu, Haoqiang

    2008-11-01

    The objective of this study is to identify high risk factors that are closely related to repeat DUI crashes using readily available information from the state crash records. Survival analysis was used and a Cox proportional hazards model was developed using the police-reported crash records in the state of Louisiana. A variety of variables were found to be significant in predicting repeat DUI crashes. The factors included the characteristics of the drivers (gender, race, and age), the types of the vehicle (light truck/pick up truck or other), the characteristics of the crash (hit-and-run, driver violations, and whether the driver is arrested), the type of location (residential area or other), and the characteristics of the roadway (highway type and roadway type). This study provides a comprehensive picture of the repeat DUI crashes. The model can quantitatively predict the relative hazards of repeat DUI crashes. It can be used to identify the characteristics of the crash-involved DUI drivers who are at greatest risk of being involved in a subsequent DUI crash, allowing to apply appropriate remedial measures to reduce the risk.

  15. Repeated Instant Self-healing Shape Memory Composites

    NASA Astrophysics Data System (ADS)

    Wang, C. C.; Ding, Z.; Purnawali, H.; Huang, W. M.; Fan, H.; Sun, L.

    2012-12-01

    We present a shape memory composite which is made of two types of shape memory materials, namely shape memory alloy (SMA) and shape memory hybrid. This composite has repeated instant self-healing function by means of not only shape recovery but also strength recovery (over 80%). The activation of the self-healing function is triggered by joule heating the embedded SMA.

  16. Problem Solving with Guided Repeated Oral Reading Instruction

    ERIC Educational Resources Information Center

    Conderman, Greg; Strobel, Debra

    2006-01-01

    Many students with disabilities require specialized instructional interventions and frequent progress monitoring in reading. The guided repeated oral reading technique promotes oral reading fluency while providing a reliable data-based monitoring system. This article emphasizes the importance of problem-solving when using this reading approach.

  17. The development of ingroup favoritism in repeated social dilemmas

    PubMed Central

    Dorrough, Angela R.; Glöckner, Andreas; Hellmann, Dshamilja M.; Ebert, Irena

    2015-01-01

    In two comprehensive and fully incentivized studies, we investigate the development of ingroup favoritism as one of two aspects of parochial altruism in repeated social dilemmas. Specifically, we test whether ingroup favoritism is a fixed phenomenon that can be observed from the very beginning and remains stable over time, or whether it develops (increases vs. decreases) during repeated contact. Ingroup favoritism is assessed through cooperation behavior in a repeated continuous prisoner's dilemma where participants sequentially interact with 10 members of the ingroup (own city and university) and subsequently with 10 members of the outgroup (other city and university), or vice versa. In none of the experiments do we observe initial differences in cooperation behavior for interaction partners from the ingroup, as compared to outgroup, and we only observe small differences in expectations regarding the interaction partners' cooperation behavior. After repeated interaction, however, including a change of groups, clear ingroup favoritism can be observed. Instead of being due to gradual and potentially biased updating of expectations, we found that these emerging differences were mainly driven by the change of interaction partners' group membership that occurred after round 10. This indicates that in social dilemma settings ingroup favoritism is to some degree dynamic in that it is enhanced and sometimes only observable if group membership is activated by thinking about both the interaction with the ingroup and the outgroup. PMID:25972821

  18. Active Listening--Listen, Repeat, Do. Scans Plans Portfolio.

    ERIC Educational Resources Information Center

    Sample, Barbara

    In this unit, students will use active listening, repeating, or paraphrasing what has been said to confirm understanding and introductory phrases and rising intonation to ask for clarification. They will also follow one, two, or multi-step instructions or give instructions to another person. (Adjunct ERIC Clearinghouse for ESL Literacy Education)…

  19. Repeating Input-Based Tasks with Young Beginner Learners

    ERIC Educational Resources Information Center

    Shintani, Natsuko

    2012-01-01

    The study reported in this article investigated task-repetition with young Japanese children. Fifteen children with no prior knowledge of English completed a communicative listening task that was designed to introduce new vocabulary. The same task was repeated nine times over five weeks. In line with Allwright's (1984) claim that "interaction…

  20. A Deluge of Complex Repeats: The Solanum Genome

    PubMed Central

    Mehra, Mrigaya; Gangwar, Indu; Shankar, Ravi

    2015-01-01

    Repetitive elements have lately emerged as key components of genome, performing varieties of roles. It has now become necessary to have an account of repeats for every genome to understand its dynamics and state. Recently, genomes of two major Solanaceae species, Solanum tuberosum and Solanum lycopersicum, were sequenced. These species are important crops having high commercial significance as well as value as model species. However, there is a reasonable gap in information about repetitive elements and their possible roles in genome regulation for these species. The present study was aimed at detailed identification and characterization of complex repetitive elements in these genomes, along with study of their possible functional associations as well as to assess possible transcriptionally active repetitive elements. In this study, it was found that ~50–60% of genomes of S. tuberosum and S. lycopersicum were composed of repetitive elements. It was also found that complex repetitive elements were associated with >95% of genes in both species. These two genomes are mostly composed of LTR retrotransposons. Two novel repeat families very similar to LTR/ERV1 and LINE/RTE-BovB have been reported for the first time. Active existence of complex repeats was estimated by measuring their transcriptional abundance using Next Generation Sequencing read data and Microarray platforms. A reasonable amount of regulatory components like transcription factor binding sites and miRNAs appear to be under the influence of these complex repetitive elements in these species, while several genes appeared to possess exonized repeats. PMID:26241045

  1. Beyond Repeat after Me: Teaching Pronunciation to English Learners

    ERIC Educational Resources Information Center

    Yoshida, Marla Tritch

    2016-01-01

    This engaging text clearly presents essential concepts that teachers need to guide their students toward clearly intelligible pronunciation and more effective communication skills. Based on a sound theoretical background, the book presents practical, imaginative ways to teach and practice pronunciation that go beyond simple "Repeat after…

  2. Repeated Reading Intervention Effects in Kindergartners with Partial Letter Knowledge

    ERIC Educational Resources Information Center

    van Gorp, Karly; Segers, Eliane; Verhoeven, Ludo

    2014-01-01

    The direct, transfer and retention effects of a repeated reading intervention study of single CVC (consonant in the onset and a vowel and consonant in the rime) words in kindergartners with partial letter knowledge were examined. A total of 26 second-year kindergartners participated in this study. Participants were divided over two feedback…

  3. Experimentally Induced Repeated Anhydrobiosis in the Eutardigrade Richtersius coronifer

    PubMed Central

    2016-01-01

    Tardigrades represent one of the main animal groups with anhydrobiotic capacity at any stage of their life cycle. The ability of tardigrades to survive repeated cycles of anhydrobiosis has rarely been studied but is of interest to understand the factors constraining anhydrobiotic survival. The main objective of this study was to investigate the patterns of survival of the eutardigrade Richtersius coronifer under repeated cycles of desiccation, and the potential effect of repeated desiccation on size, shape and number of storage cells. We also analyzed potential change in body size, gut content and frequency of mitotic storage cells. Specimens were kept under non-cultured conditions and desiccated under controlled relative humidity. After each desiccation cycle 10 specimens were selected for analysis of morphometric characteristics and mitosis. The study demonstrates that tardigrades may survive up to 6 repeated desiccations, with declining survival rates with increased number of desiccations. We found a significantly higher proportion of animals that were unable to contract properly into a tun stage during the desiccation process at the 5th and 6th desiccations. Also total number of storage cells declined at the 5th and 6th desiccations, while no effect on storage cell size was observed. The frequency of mitotic storage cells tended to decline with higher number of desiccation cycles. Our study shows that the number of consecutive cycles of anhydrobiosis that R. coronifer may undergo is limited, with increased inability for tun formation and energetic constraints as possible causal factors. PMID:27828978

  4. The Analysis of Repeated Measures Designs Involving Multiple Dependent Variables.

    ERIC Educational Resources Information Center

    Schutz, Robert W.; Gessaroli, Marc E.

    1987-01-01

    The article discusses the concepts and interpretations for four methods of testing differences among means in a mixed model repeated measures design. The four methods discussed are: traditional ANOVA and the MANOVA methods for the single dependent variable case, and a Multivariate Mixed Model analysis and a Doubly Multivariate analysis for the…

  5. Genome Wide Characterization of Simple Sequence Repeats in Cucumber

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The whole genome sequence of the cucumber cultivar Gy14 was recently sequenced at 15× coverage with the Roche 454 Titanium technology. The microsatellite DNA sequences (simple sequence repeats, SSRs) in the assembled scaffolds were computationally explored and characterized. A total of 112,073 SSRs ...

  6. Response of two prairie forbs to repeated vole herbivory.

    PubMed

    Sullivan, Amy T; Howe, Henry F

    2011-04-01

    Vertebrate herbivores as diverse as ungulates, geese, and rabbits preferentially feed on plants that have previously experienced herbivory. Here, we ask whether smaller grassland "cryptic consumers" such as voles (Microtus ochrogaster and M. pennsylvanicus) preferentially clip (cut stems for access to leaves or seeds) or avoid previously clipped individuals of two tallgrass prairie species (Desmanthus illinoensis and Echinacea purpurea) within a growing season. Further, we ask how these plants respond to repeated clipping within a growing season, and whether the effects of this herbivory last into the subsequent growing season. Voles preferentially clipped stems of D. illinoensis and E. purpurea plants that had been previously clipped. The exception was indiscriminant clipping of stems of E. purpurea late in the growing season when its achenes, a favorite vole food, ripened. For D. illinoensis, repeated clipping resulted in a 59% reduction in biomass, 42% lower ratio of reproductive to vegetative biomass, and 57% fewer seeds produced per plant compared with unclipped plants. These effects lasted into the following growing season in which plants were protected from voles. In contrast, the only effect of repeated clipping for E. purpurea was that the number of achenes per plant was substantially reduced by three episodes of clipping. This effect did not carry over to the next growing season. Such differences in D. illinoensis and E. purpurea response to repeated stem clipping by voles offer insights into how these small rodents can effect major changes in composition and dominance in grassland communities.

  7. Teaching the Repeated Prisoner's Dilemma with a Computerized Tournament

    ERIC Educational Resources Information Center

    Lange, Carsten; Baylor, Amy L.

    2007-01-01

    The authors present a constructivist approach for teaching game theory, on the basis, in part, of Axelrod's research approach. Using the Axelrod tournament multi-user system (ATMUS) software, students create strategies for a repeated prisoner's dilemma (RPD). Later, these strategies are matched with those of their classmates' in a classroom…

  8. Repeated Interviews with Children Who Have Intellectual Disabilities

    ERIC Educational Resources Information Center

    Cederborg, A.-C.; La Rooy, D.; Lamb, M. E.

    2008-01-01

    Background: We predicted that repeated interviewing would improve the informativeness of children with intellectual disabilities who were questioned in criminal investigations. Materials: The chronological ages of the 19 children, involved in 20 cases, ranged between 4.7 and 18 years (M = 10.3 years) at the time of the first alleged abuse. Method:…

  9. 47 CFR 90.247 - Mobile repeater stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... repeaters and/or associated hand-carried transmitters may be assigned separate base/mobile frequencies for... with one or more base stations. (f) When automatically retransmitting messages originated by or... access signal can be achieved by use of digital or analog methods....

  10. 47 CFR 90.247 - Mobile repeater stations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... repeaters and/or associated hand-carried transmitters may be assigned separate base/mobile frequencies for... with one or more base stations. (f) When automatically retransmitting messages originated by or... access signal can be achieved by use of digital or analog methods....

  11. 47 CFR 90.247 - Mobile repeater stations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... repeaters and/or associated hand-carried transmitters may be assigned separate base/mobile frequencies for... with one or more base stations. (f) When automatically retransmitting messages originated by or... access signal can be achieved by use of digital or analog methods....

  12. 47 CFR 90.247 - Mobile repeater stations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... repeaters and/or associated hand-carried transmitters may be assigned separate base/mobile frequencies for... with one or more base stations. (f) When automatically retransmitting messages originated by or... access signal can be achieved by use of digital or analog methods....

  13. Results of 1993 Repeat-Pass SAR Interferometry Experiments

    NASA Technical Reports Server (NTRS)

    Klein, J. D.; Hensley, S.; Madsen, S. N.; Webb, F. H.

    1994-01-01

    In this talk we present results of a repeat-pass SAR interferometry experiment performed in June 1993 near Portage, Maine. Differential GPS data accurate to +/-10cm were acquired to aid in motion compensation and geolocation of targets in the imagery. The experiment and data analysis will be discussed, and results will be shown during the presentation.

  14. Validity of repeated initial rise thermoluminescence kinetic parameter determinations

    SciTech Connect

    Kierstead, J.A.; Levy, P.W.

    1990-01-01

    The validity of thermoluminescence (TL) analysis by repeated initial rise measurements has been studied by computer simulation. Thermoluminescence described by 1st Order, 2nd Order, General One Trap and Interactive TL Kinetics was investigated. In the simulation each of the repeated temperature increase and decrease cycles contains a linear temperature increase followed by a decrease appropriate for radiative cooling, i.e. the latter is approximated by a decreasing exponential. The activation energies computed from the simulated emission are readily compared with those used to compute the TL emission. In all cases studied, the repeated initial rise technique provides reliable results only for single peak glow curves or for glow curves containing peaks that do not overlap and, if sufficiently separated, the lowest temperature peak in multipeak curves. Also the temperatures, or temperature cycles corresponding to correct activation energies occur on the low temperature side of the normal glow curve, often well below the peak temperature. A variety of misleading and/or incorrect results an be obtained when the repeated initial rise technique is applied to TL systems that produce overlapping peaks in the usual glow curve. 6 refs., 10 figs.

  15. Simple sequence repeat markers that identify Claviceps species and strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Claviceps purpurea is a pathogen that infects most members of the Pooideae subfamily and causes ergot, a floral disease in which the ovary is replaced with a sclerotium. This study was initiated to develop Simple Sequence Repeat (SSRs) markers for rapid identification of C. purpurea. SSRs were desi...

  16. Parameter estimation and infiltration tests at the repeat facility

    NASA Astrophysics Data System (ADS)

    Burns, P.; Armstrong, P.; Winn, B.

    1983-11-01

    Work performed in the reconfigurable passive evaluation analysis and test (REPEAT) facility is reviewed. The physical characteristics of the building and the instrumentation are described. Collected data are discussed. Treatment of parameter estimation ensures with example calculations. Infiltration instrumentation and tests are described. Flow visualization studies are discussed.

  17. Repeated administration of adenosine increases its cardiovascular effects in rats.

    PubMed

    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  18. Mourning and Guilt among Greek Women Having Repeated Abortions.

    ERIC Educational Resources Information Center

    Naziri, D.; Tzavaras, A.

    1993-01-01

    Conducted clinical study concerning bereavement process of Greek women after abortion. Found strong identificatory tendencies on both mother and father images. Argues that, in cases of repeated abortion, mourning and guilt do not only refer to murdered and lost "person-fetus" but principally to death and loss of object of ambiguous…

  19. A Comparison of Pairs Figure Skaters in Repeated Jumps

    PubMed Central

    Sands, William A.; Kimmel, Wendy L.; McNeal, Jeni R.; Murray, Steven Ross; Stone, Michael H.

    2012-01-01

    Trends in pairs figure skating have shown that increasingly difficult jumps have become an essential aspect of high-level performance, especially in the latter part of a competitive program. We compared a repeated jump power index in a 60 s repeated jump test to determine the relationship of repeated jump test to competitive rank and to measure 2D hip, knee, and ankle angles and angular velocities at 0, 20, 40, and 60 s. Eighteen National Team Pairs Figure Skaters performed a 60 s repeated jump test on a large switch-mat with timing of flight and ground durations and digital video recording. Each 60-s period was divided into 6, 10-s intervals, with power indexes (W/kg) calculated for each 10-s interval. Power index by 10-s interval repeated measures ANOVAs (RMANOVA) showed that males exceeded females at all intervals, and the highest power index interval was during 10 to 20 s for both sexes. RMANOVAs of angles and angular velocities showed main effects for time only. Power index and jumping techniques among figure skaters showed rapid and steady declines over the test duration. Power index can predict approximately 50% of competitive rank variance, and sex differences in jumping technique were rare. Key pointsThe repeated jumps test can account for about 50% of the variance in pairs ranks.Changes in technique are largely due to fatigue, but the athletes were able to maintain a maximum flexion knee angle very close to the desired 90 degrees. Changes in angular velocity and jump heights occurred as expected, again probably due to fatigue.As expected from metabolic information, the athletes' power indexes peak around 20s and decline thereafter. Coaches should be aware of this time as a boundary beyond which fatigue becomes more manifest, and use careful choreographic choices to provide rest periods that are disguised as less demanding skating elements to afford recovery.The repeated jumps test may be a helpful off-ice test of power-endurance for figure skaters. PMID

  20. A comparison of pairs figure skaters in repeated jumps.

    PubMed

    Sands, William A; Kimmel, Wendy L; McNeal, Jeni R; Murray, Steven Ross; Stone, Michael H

    2012-01-01

    Trends in pairs figure skating have shown that increasingly difficult jumps have become an essential aspect of high-level performance, especially in the latter part of a competitive program. We compared a repeated jump power index in a 60 s repeated jump test to determine the relationship of repeated jump test to competitive rank and to measure 2D hip, knee, and ankle angles and angular velocities at 0, 20, 40, and 60 s. Eighteen National Team Pairs Figure Skaters performed a 60 s repeated jump test on a large switch-mat with timing of flight and ground durations and digital video recording. Each 60-s period was divided into 6, 10-s intervals, with power indexes (W/kg) calculated for each 10-s interval. Power index by 10-s interval repeated measures ANOVAs (RMANOVA) showed that males exceeded females at all intervals, and the highest power index interval was during 10 to 20 s for both sexes. RMANOVAs of angles and angular velocities showed main effects for time only. Power index and jumping techniques among figure skaters showed rapid and steady declines over the test duration. Power index can predict approximately 50% of competitive rank variance, and sex differences in jumping technique were rare. Key pointsThe repeated jumps test can account for about 50% of the variance in pairs ranks.Changes in technique are largely due to fatigue, but the athletes were able to maintain a maximum flexion knee angle very close to the desired 90 degrees. Changes in angular velocity and jump heights occurred as expected, again probably due to fatigue.As expected from metabolic information, the athletes' power indexes peak around 20s and decline thereafter. Coaches should be aware of this time as a boundary beyond which fatigue becomes more manifest, and use careful choreographic choices to provide rest periods that are disguised as less demanding skating elements to afford recovery.The repeated jumps test may be a helpful off-ice test of power-endurance for figure skaters.

  1. Evolution Analysis of Simple Sequence Repeats in Plant Genome.

    PubMed

    Qin, Zhen; Wang, Yanping; Wang, Qingmei; Li, Aixian; Hou, Fuyun; Zhang, Liming

    2015-01-01

    Simple sequence repeats (SSRs) are widespread units on genome sequences, and play many important roles in plants. In order to reveal the evolution of plant genomes, we investigated the evolutionary regularities of SSRs during the evolution of plant species and the plant kingdom by analysis of twelve sequenced plant genome sequences. First, in the twelve studied plant genomes, the main SSRs were those which contain repeats of 1-3 nucleotides combination. Second, in mononucleotide SSRs, the A/T percentage gradually increased along with the evolution of plants (except for P. patens). With the increase of SSRs repeat number the percentage of A/T in C. reinhardtii had no significant change, while the percentage of A/T in terrestrial plants species gradually declined. Third, in dinucleotide SSRs, the percentage of AT/TA increased along with the evolution of plant kingdom and the repeat number increased in terrestrial plants species. This trend was more obvious in dicotyledon than monocotyledon. The percentage of CG/GC showed the opposite pattern to the AT/TA. Forth, in trinucleotide SSRs, the percentages of combinations including two or three A/T were in a rising trend along with the evolution of plant kingdom; meanwhile with the increase of SSRs repeat number in plants species, different species chose different combinations as dominant SSRs. SSRs in C. reinhardtii, P. patens, Z. mays and A. thaliana showed their specific patterns related to evolutionary position or specific changes of genome sequences. The results showed that, SSRs not only had the general pattern in the evolution of plant kingdom, but also were associated with the evolution of the specific genome sequence. The study of the evolutionary regularities of SSRs provided new insights for the analysis of the plant genome evolution.

  2. Conservative Sample Size Determination for Repeated Measures Analysis of Covariance.

    PubMed

    Morgan, Timothy M; Case, L Douglas

    2013-07-05

    In the design of a randomized clinical trial with one pre and multiple post randomized assessments of the outcome variable, one needs to account for the repeated measures in determining the appropriate sample size. Unfortunately, one seldom has a good estimate of the variance of the outcome measure, let alone the correlations among the measurements over time. We show how sample sizes can be calculated by making conservative assumptions regarding the correlations for a variety of covariance structures. The most conservative choice for the correlation depends on the covariance structure and the number of repeated measures. In the absence of good estimates of the correlations, the sample size is often based on a two-sample t-test, making the 'ultra' conservative and unrealistic assumption that there are zero correlations between the baseline and follow-up measures while at the same time assuming there are perfect correlations between the follow-up measures. Compared to the case of taking a single measurement, substantial savings in sample size can be realized by accounting for the repeated measures, even with very conservative assumptions regarding the parameters of the assumed correlation matrix. Assuming compound symmetry, the sample size from the two-sample t-test calculation can be reduced at least 44%, 56%, and 61% for repeated measures analysis of covariance by taking 2, 3, and 4 follow-up measures, respectively. The results offer a rational basis for determining a fairly conservative, yet efficient, sample size for clinical trials with repeated measures and a baseline value.

  3. Source Parameters for Repeating Earthquakes along the Middle America Trench

    NASA Astrophysics Data System (ADS)

    Bilek, S. L.; Phillips, W. S.; Walter, J. I.; Peng, Z.; Schwartz, S. Y.; Brudzinski, M. R.; Yao, D.

    2015-12-01

    Repeating earthquakes, with their similar locations and similar waveforms, are often thought to represent slip along the same patch of fault. Analysis of these earthquake clusters can provide useful information about the nature of the fault and earthquake interaction. Here we focus on sequences of repeating earthquakes along both the Nicoya Peninsula, Costa Rica and along the Oaxaca segment of Mexico, as both megathrust faults have been well instrumented in recent years with local seismic networks able to record the small magnitude earthquakes. These regions have also experienced large megathrust earthquakes as well as non-volcanic tremor and slow slip, suggesting a complex fault system that allows a wide spectrum of slip. We can use source characteristics of the repeating earthquakes to probe this fault complexity. Along the Nicoya Peninsula, there are over 370 repeating earthquakes (M 0.5-3.3) in the 3 months following the 2012 Mw 7.6 megathrust earthquake grouped into 55 distinct clusters. Along Oaxaca, the earthquake clusters or swarms (M 1.5-5.5) span a wider spatial and temporal range. For our source parameter calculations, we form narrow-frequency band envelopes for pairs of earthquakes within the earthquake clusters to compute spectral ratios for each pair. We determine seismic moment, corner frequency, and earthquake stress drop for each earthquake from these spectral ratios. We compare the source parameters for events within the clusters to examine temporal variations and compare between clusters to explore spatial variations that could be linked to other slip heterogeneity. Preliminary results for the Nicoya region suggest nearly identical stress drop for repeating events within clusters located near the 2012 mainshock, and more variability in stress drops for earthquakes in clusters located updip and to the northwest of the mainshock.

  4. Repeatability and reliability of human eye in visual shade selection.

    PubMed

    Özat, P B; Tuncel, İ; Eroğlu, E

    2013-12-01

    Deficiencies in the human visual percep-tion system have challenged the efficiency of the visual shade-matching protocol. The aim of this study was to evaluate the repeatability and reliability of human eye in visual shade selection. Fifty-four volunteering dentists were asked to match the shade of an upper right central incisor tooth of a single subject. The Vita 3D-Master shade guide was used for the protocol. Before each shade-matching procedure, the definitive codes of the shade tabs were hidden by an opaque strip and the shade tabs were placed into the guide randomly. The procedure was repeated 1 month later to ensure that visual memory did not affect the results. The L*, a* and b* values of the shade tabs were measured with a dental spectrophotometer (Vita Easyshade) to produce quantitative values to evaluate the protocol. The paired samples t-test and Pearson correlation test were used to compare the 1st and 2nd selections. The Yates-corrected chi-square test was use to compare qualitative values. Statistical significance was accepted at P < 0·05. Comparing baseline and 1st month records, statistical significance (P < 0·001) was found among qualitative data regarding repeatability on a yes/no (1/0) basis, revealing a very low percentage of repeatability (11·1%). Comparing baseline and 1st month records, statistical significance was not found (P = 0·000) among the L*, a*, b* and ΔE variables. These results indicate that dentists perform insufficiently regarding repeatability in visual shade matching, but they are able to select clinically acceptable shades.

  5. Practical use of the repeating patterns in mask writing

    NASA Astrophysics Data System (ADS)

    Shoji, Masahiro; Inoue, Tadao; Yamabe, Masaki

    2010-03-01

    In May 2006, the Mask Design, Drawing, and Inspection Technology Research Department (Mask D2I) at the Association of Super-Advanced Electronics Technologies (ASET) launched a 4-year program for reducing mask manufacturing cost and TAT by concurrent optimization of MDP, mask writing, and mask inspection. As one of the tasks being pursued at the Mask Design Data Technology Research Laboratory, we have evaluated the effect of reducing the drawing shot counts by utilizing the repeating patterns, and showed positive impact on mask making by using CP drawing. During the past four years, we have developed a software to extract repeating patterns from fractured OPCed mask data which can be used to minimize the shot counts. In this evaluation, we have used an actual device production data obtained from the member companies of MaskD2I. To the extraction software we added new functions for extracting common repeating patterns from a set of multiple masks, and studied how this step can reduce the counts in comparison to the shot counts required during the conventional mask writing techniques. We have also developed software that uses the extraction result of repeating patterns and prepares drawing-data for the MCC/CP drawing system, which has been developed at the Mask Writing Equipment Technology Research Laboratory. With this software, we have simulated EB proximity effect on CP writing and examined how it affect the shot count reduction where CP shots with large CD errors are to be divided into VSB shots. In this paper, we will report the evaluation result of the practical application of repeating patterns in mask writing with this software.

  6. Comparison of Repeated and Non-Repeated Readings on the Reading Performances of Students with Emotional and Behavioral Disorders

    ERIC Educational Resources Information Center

    Escarpio, Raul; Barbetta, Patricia M.

    2016-01-01

    This study used an alternating treatments design to compare the effects of three conditions on the reading fluency, errors, and comprehension of four, sixth-grade students with emotional and behavioral disorders (EBD) who were struggling readers. The conditions were (a) repeated readings in which participants read three times a passage of 100 or…

  7. Base excision repair of oxidative DNA damage coupled with removal of a CAG repeat hairpin attenuates trinucleotide repeat expansion.

    PubMed

    Xu, Meng; Lai, Yanhao; Torner, Justin; Zhang, Yanbin; Zhang, Zunzhen; Liu, Yuan

    2014-04-01

    Trinucleotide repeat (TNR) expansion is responsible for numerous human neurodegenerative diseases. However, the underlying mechanisms remain unclear. Recent studies have shown that DNA base excision repair (BER) can mediate TNR expansion and deletion by removing base lesions in different locations of a TNR tract, indicating that BER can promote or prevent TNR expansion in a damage location-dependent manner. In this study, we provide the first evidence that the repair of a DNA base lesion located in the loop region of a CAG repeat hairpin can remove the hairpin, attenuating repeat expansion. We found that an 8-oxoguanine located in the loop region of CAG hairpins of varying sizes was removed by OGG1 leaving an abasic site that was subsequently 5'-incised by AP endonuclease 1, introducing a single-strand breakage in the hairpin loop. This converted the hairpin into a double-flap intermediate with a 5'- and 3'-flap that was cleaved by flap endonuclease 1 and a 3'-5' endonuclease Mus81/Eme1, resulting in complete or partial removal of the CAG hairpin. This further resulted in prevention and attenuation of repeat expansion. Our results demonstrate that TNR expansion can be prevented via BER in hairpin loops that is coupled with the removal of TNR hairpins.

  8. Calibration of mutation rates reveals diverse subfamily structure of galliform CR1 repeats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CR1 repeats are the most abundant family of repeats in the chicken genome, with more than 200,000 copies accounting for ~80% of the chicken interspersed repeats. CR1 repeats are believed to have arisen from the retrotransposition of a small number of master elements, which gave rise to the 22 CR1 su...

  9. Simple sequence repeat markers useful for sorghum downy mildew (Peronosclerospora sorghi) and related species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Among the 55 primers pairs designed from clones from pathotype 3 of P. sorghi, 36 flanked microsatellite loci containing simple repeats, including 28 (55%) with dinucleotide repeats and 6 (11%) with trinucleotide repeats. A total of 22 microsatellites with CA/AC or GT/TG repeats were the most abund...

  10. 40 CFR 141.858 - Repeat monitoring and E. coli requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... exceeded. (b) Escherichia coli (E. coli) testing. (1) If any routine or repeat sample is total coliform... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Repeat monitoring and E. coli....858 Repeat monitoring and E. coli requirements. (a) Repeat monitoring. (1) If a sample taken...

  11. 40 CFR 141.858 - Repeat monitoring and E. coli requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... exceeded. (b) Escherichia coli (E. coli) testing. (1) If any routine or repeat sample is total coliform... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Repeat monitoring and E. coli....858 Repeat monitoring and E. coli requirements. (a) Repeat monitoring. (1) If a sample taken...

  12. Microevolution of pandemic Vibrio parahaemolyticus assessed by the number of repeat units in short sequence tandem repeat regions.

    PubMed

    García, Katherine; Gavilán, Ronnie G; Höfle, Manfred G; Martínez-Urtaza, Jaime; Espejo, Romilio T

    2012-01-01

    The emergence of the pandemic strain Vibrio parahaemolyticus O3:K6 in 1996 caused a large increase of diarrhea outbreaks related to seafood consumption in Southeast Asia, and later worldwide. Isolates of this strain constitutes a clonal complex, and their effectual differentiation is possible by comparison of their variable number tandem repeats (VNTRs). The differentiation of the isolates by the differences in VNTRs will allow inferring the population dynamics and microevolution of this strain but this requires knowing the rate and mechanism of VNTRs' variation. Our study of mutants obtained after serial cultivation of clones showed that mutation rates of the six VNTRs examined are on the order of 10(-4) mutant per generation and that difference increases by stepwise addition of single mutations. The single stepwise mutation (SSM) was deduced because mutants with 1, 2, 3, or more repeat unit deletions or insertions follow a geometric distribution. Plausible phylogenetic trees are obtained when, according to SSM, the genetic distance between clusters with different number of repeats is assessed by the absolute differences in repeats. Using this approach, mutants originated from different isolates of pandemic V. parahaemolyticus after serial cultivation are clustered with their parental isolates. Additionally, isolates of pandemic V. parahaemolyticus from Southeast Asia, Tokyo, and northern and southern Chile are clustered according their geographical origin. The deepest split in these four populations is observed between the Tokyo and southern Chile populations. We conclude that proper phylogenetic relations and successful tracing of pandemic V. parahaemolyticus requires measuring the differences between isolates by the absolute number of repeats in the VNTRs considered.

  13. Fully integrated, fully automated generation of short tandem repeat profiles

    PubMed Central

    2013-01-01

    Background The generation of short tandem repeat profiles, also referred to as ‘DNA typing,’ is not currently performed outside the laboratory because the process requires highly skilled technical operators and a controlled laboratory environment and infrastructure with several specialized instruments. The goal of this work was to develop a fully integrated system for the automated generation of short tandem repeat profiles from buccal swab samples, to improve forensic laboratory process flow as well as to enable short tandem repeat profile generation to be performed in police stations and in field-forward military, intelligence, and homeland security settings. Results An integrated system was developed consisting of an injection-molded microfluidic BioChipSet cassette, a ruggedized instrument, and expert system software. For each of five buccal swabs, the system purifies DNA using guanidinium-based lysis and silica binding, amplifies 15 short tandem repeat loci and the amelogenin locus, electrophoretically separates the resulting amplicons, and generates a profile. No operator processing of the samples is required, and the time from swab insertion to profile generation is 84 minutes. All required reagents are contained within the BioChipSet cassette; these consist of a lyophilized polymerase chain reaction mix and liquids for purification and electrophoretic separation. Profiles obtained from fully automated runs demonstrate that the integrated system generates concordant short tandem repeat profiles. The system exhibits single-base resolution from 100 to greater than 500 bases, with inter-run precision with a standard deviation of ±0.05 - 0.10 bases for most alleles. The reagents are stable for at least 6 months at 22°C, and the instrument has been designed and tested to Military Standard 810F for shock and vibration ruggedization. A nontechnical user can operate the system within or outside the laboratory. Conclusions The integrated system represents the

  14. Repeat Lumbar Punctures in Infants with Meningitis in the Neonatal Intensive Care Unit

    PubMed Central

    Greenberg, Rachel G.; Benjamin, Daniel K.; Cohen-Wolkowiez, Michael; Clark, Reese H.; Cotten, C. Michael; Laughon, Matthew; Smith, P. Brian

    2010-01-01

    Objective The purpose of this study is to examine the results of repeat lumbar puncture in infants with initial positive cerebrospinal fluid (CSF) cultures in order to determine the clinical characteristics and outcomes of infants with repeat positive cultures. Study Design Cohort study of infants with an initial positive CSF culture undergoing repeat lumbar puncture between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. We compared the clinical outcomes of infants with repeat positive cultures and infants with repeat negative cultures. Result We identified 118 infants with repeat CSF cultures. Of these, 26 infants had repeat positive cultures. A higher proportion with repeat positive cultures died compared to those with repeat negative cultures, 6/23 (26%) vs. 6/81 (7%), respectively (p=0.02). Conclusion Among infants with a positive CSF culture, a repeat positive CSF culture is common. The presence of a second positive culture is associated with increased mortality. PMID:21164430

  15. The Student Volunteer Army: a 'repeat emergent' emergency response organisation.

    PubMed

    Carlton, Sally; Mills, Colleen E

    2017-01-17

    This paper seeks to contribute to understanding of the factors associated with an effective emergent emergency response organisation and to provide new insights into this understudied area. It examines, through an analysis of a range of textual resources, the emergence and re-emergence of the Student Volunteer Army (SVA) during the devastating earthquakes in Canterbury, New Zealand, in 2010-11. This evaluation is conducted in relation to the four key features of an effective emergency response organisation: adaptability; direction; leadership; and communication. In addition, the paper aims to further understanding of 'emergency entrepreneurship' and thus of the values and strategies that underpin social entrepreneur organisations in times of normalcy. The paper concludes that the unique position of the SVA as a 'repeat emergent' emergency response organisation enabled it to innovate continually and to improve repeatedly its systems, relationships, and image, such that it exhibited features common to emergent and established emergency response organisations.

  16. Item repetition in short-term memory: Ranschburg repeated.

    PubMed

    Henson, R N

    1998-09-01

    In serial recall from short-term memory, repeated items are recalled well when close together (repetition facilitation), but not when far apart (repetition inhibition; the Ranschburg effect). These effects were re-examined with a new scoring scheme that addresses the possibility that repetitions are distinct tokens in memory. Repetition facilitation and repetition inhibition proved robust, and were shown to interact with the temporal grouping of items (Experiment 1), which affected the probability of detecting repetition (Experiments 2A and 2B). It is argued that detection of a repetition is necessary for repetition facilitation, attributable to the tagging of immediate repetition, whereas the failure to detect or remember a repetition results in repetition inhibition, attributable to an automatic suppression of previous responses and a bias against guessing repeated items (Experiment 3). The findings are discussed in relation to models of short-term memory and the phenomenon of repetition blindness.

  17. Repeated Names, Overt Pronouns, and Null Pronouns in Spanish

    PubMed Central

    Lezama, Carlos Gelormini; Almor, Amit

    2010-01-01

    In two self-paced, sentence-by-sentence reading experiments we examined the difference in the processing of Spanish discourses with repeated names, overt pronouns, and null pronouns in emphatic and non-emphatic contexts. In Experiment 1, repeated names and overt pronouns caused a processing delay when they referred to salient antecedents in non-emphatic contexts. In Experiment 2, both processing delays were eliminated when an emphatic cleft-structure was used. The processing delay caused by overt pronouns referring to salient antecedents in non-emphatic contexts in Spanish contrasts with previous findings in Chinese, where null and overt pronouns elicited similar reading times. We explain both our Spanish findings and the Chinese findings in a unified framework based on the notion of balance between processing cost and discourse function in line with the Informational Load Hypothesis. PMID:21552376

  18. Mammalian microRNAs derived from genomic repeats.

    PubMed

    Smalheiser, Neil R; Torvik, Vetle I

    2005-06-01

    In this article, we show that a subset of conventional mammalian microRNAs is derived from LINE-2 transposable elements and other genome repeats. These repeat-derived microRNAs arise from conventional precursor hairpins and are distinct from the rasiRNAs, which appear to be processed from long double-stranded RNA precursors. The insertion of transposable elements into new genomic sites appears to be one of the driving-forces that create new microRNAs during mammalian evolution. Two of the LINE-2-derived microRNAs exhibit perfect complementarity to a large family of mRNA and EST transcripts that contain portions of MIR and other LINE-2 elements in their 3'-untranslated regions.

  19. Repeated probing of Southwestern blots using alkaline phosphatase stripping.

    PubMed

    Jia, Yinshan; Jiang, Daifeng; Jarrett, Harry W

    2010-11-05

    Southwestern blotting is when a DNA sequence is used to probe DNA-binding proteins on an electrophoretic gel blot. It would be highly desirable to be able to probe a blot repeatedly with different DNA sequences. Alkaline phosphatase can remove 5'-phosphoryl groups from DNA and radiolabeled 5'-(32)P-DNA probes are commonly used in Southwestern blotting. Here is shown that once probed, the radioisotope signal on the blot can be effectively removed by brief digestion with alkaline phosphatase, and the blot can then be repeatedly probed at least six times with different DNA probes. This exceeds the repetitions possible with another commonly used method using SDS. The technique can be used with either one-dimensional or multi-dimensional Southwestern blots and does not have a large effect on the phosphorylation state of the blotted proteins. An alternative method using T4 polynucleotide kinase stripping is also introduced but was less well characterized.

  20. A high stability and repeatability electrochemical scanning tunneling microscope

    SciTech Connect

    Xia, Zhigang; Wang, Jihao; Lu, Qingyou; Hou, Yubin

    2014-12-15

    We present a home built electrochemical scanning tunneling microscope (ECSTM) with very high stability and repeatability. Its coarse approach is driven by a closely stacked piezo motor of GeckoDrive type with four rigid clamping points, which enhances the rigidity, compactness, and stability greatly. It can give high clarity atomic resolution images without sound and vibration isolations. Its drifting rates in XY and Z directions in solution are as low as 84 pm/min and 59 pm/min, respectively. In addition, repeatable coarse approaches in solution within 2 mm travel distance show a lateral deviation less than 50 nm. The gas environment can be well controlled to lower the evaporation rate of the cell, thus reducing the contamination and elongating the measurement time. Atomically resolved SO{sub 4}{sup 2−} image on Au (111) work electrode is demonstrated to show the performance of the ECSTM.

  1. SGR-like behaviour of the repeating FRB 121102

    NASA Astrophysics Data System (ADS)

    Wang, F. Y.; Yu, H.

    2017-03-01

    Fast radio bursts (FRBs) are millisecond-duration radio signals occurring at cosmological distances. However the physical model of FRBs is mystery, many models have been proposed. Here we study the frequency distributions of peak flux, fluence, duration and waiting time for the repeating FRB 121102. The cumulative distributions of peak flux, fluence and duration show power-law forms. The waiting time distribution also shows power-law distribution, and is consistent with a non-stationary Poisson process. These distributions are similar as those of soft gamma repeaters (SGRs). We also use the statistical results to test the proposed models for FRBs. These distributions are consistent with the predictions from avalanche models of slowly driven nonlinear dissipative systems.

  2. CRISPRdigger: detecting CRISPRs with better direct repeat annotations

    PubMed Central

    Ge, Ruiquan; Mai, Guoqin; Wang, Pu; Zhou, Manli; Luo, Youxi; Cai, Yunpeng; Zhou, Fengfeng

    2016-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPRs) are important genetic elements in many bacterial and archaeal genomes, and play a key role in prokaryote immune systems’ fight against invasive foreign elements. The CRISPR system has also been engineered to facilitate target gene editing in eukaryotic genomes. Using the common features of mis-annotated CRISPRs in prokaryotic genomes, this study proposed an accurate de novo CRISPR annotation program CRISPRdigger, which can take a partially assembled genome as its input. A comprehensive comparison with the three existing programs demonstrated that CRISPRdigger can recover more Direct Repeats (DRs) for CRISPRs and achieve a higher accuracy for a query genome. The program was implemented by Perl and all the parameters had default values, so that a user could annotate CRISPRs in a query genome by supplying only a genome sequence in the FASTA format. All the supplementary data are available at http://www.healthinformaticslab.org/supp/. PMID:27596864

  3. Mechanisms of trinucleotide repeat instability during human development

    PubMed Central

    McMurray, Cynthia T.

    2011-01-01

    Trinucleotide expansion underlies several human diseases. Expansion occurs during multiple stages of human development in different cell types, and is sensitive to the gender of the parent who transmits the repeats. Repair and replication models for expansions have been described, but we do not know whether the pathway involved is the same under all conditions and for all repeat tract lengths, which differ among diseases. Currently, researchers rely on bacteria, yeast and mice to study expansion, but these models differ substantially from humans. We need now to connect the dots among human genetics, pathway biochemistry and the appropriate model systems to understand the mechanism of expansion as it occurs in human disease. PMID:20953213

  4. Repeatable Hydrogen Storage using Nano-structured Graphite Materials

    NASA Astrophysics Data System (ADS)

    Kajiura, Hisashi; Kadono, Koji; Tsutsui, Shigemitsu; Murakami, Yousuke

    2004-03-01

    Repeatable hydrogen adsorption and desorption with nano-structured graphite material (NSG) was confirmed using a high-accuracy volumetric measuring apparatus at room temperature [1]. The NSG was prepared from commercially obtained graphite powder with a purity of 99.997% (GoodFellow Cambridge Ltd.) using a mechanical milling process at a pressure of 2.0 x 10-4 Pa. The untreated graphite adsorbed 0.02wt% of hydrogen, while 0.20 - 0.25wt% of hydrogen can be repeatedly adsorbed by the NSG. Measurements of the hydrogen adsorption rate at constant pressure and pore-size distribution suggest that the hydrogen molecules are adsorbed through a diffusion process into pores with a diameter less than 1 nm. [1] H.Kajiura et al., APL82(2003)1929.

  5. Activating frataxin expression by repeat-targeted nucleic acids

    PubMed Central

    Li, Liande; Matsui, Masayuki; Corey, David R.

    2016-01-01

    Friedreich's ataxia is an incurable genetic disorder caused by a mutant expansion of the trinucleotide GAA within an intronic FXN RNA. This expansion leads to reduced expression of frataxin (FXN) protein and evidence suggests that transcriptional repression is caused by an R-loop that forms between the expanded repeat RNA and complementary genomic DNA. Synthetic agents that increase levels of FXN protein might alleviate the disease. We demonstrate that introducing anti-GAA duplex RNAs or single-stranded locked nucleic acids into patient-derived cells increases FXN protein expression to levels similar to analogous wild-type cells. Our data are significant because synthetic nucleic acids that target GAA repeats can be lead compounds for restoring curative FXN levels. More broadly, our results demonstrate that interfering with R-loop formation can trigger gene activation and reveal a new strategy for upregulating gene expression. PMID:26842135

  6. The strength of laminated composite materials under repeated impact loading

    NASA Technical Reports Server (NTRS)

    Rotem, Assa

    1988-01-01

    When low velocity and energy impact is exerted on a laminated composite material, in a perpendicular direction to the plane of the laminate, invisible damage may develop. It is shown analytically and experimentally that the invisible damage occurs during the first stage of contact between the impactor and the laminate and is a result of the contact stresses. However, the residual flexural strength changes only slightly, because it depends mainly on the outer layers, and these remain undamaged. Repeated impact intensifies the damage inside the laminate and causes larger bending under equivalent impact load. Finally, when the damage is most severe, even though it is still invisible, the laminate fails because of bending on the tension side. If the repeated impact is halted before final fracture occurs the residual strength and modulus would decrease by a certain amount.

  7. Versatile communication strategies among tandem WW domain repeats

    PubMed Central

    Dodson, Emma Joy; Fishbain-Yoskovitz, Vered; Rotem-Bamberger, Shahar

    2015-01-01

    Interactions mediated by short linear motifs in proteins play major roles in regulation of cellular homeostasis since their transient nature allows for easy modulation. We are still far from a full understanding and appreciation of the complex regulation patterns that can be, and are, achieved by this type of interaction. The fact that many linear-motif-binding domains occur in tandem repeats in proteins indicates that their mutual communication is used extensively to obtain complex integration of information toward regulatory decisions. This review is an attempt to overview, and classify, different ways by which two and more tandem repeats cooperate in binding to their targets, in the well-characterized family of WW domains and their corresponding polyproline ligands. PMID:25710931

  8. Quantum repeaters based on atomic ensembles and linear optics

    NASA Astrophysics Data System (ADS)

    Sangouard, Nicolas; Simon, Christoph; de Riedmatten, Hugues; Gisin, Nicolas

    2011-01-01

    The distribution of quantum states over long distances is limited by photon loss. Straightforward amplification as in classical telecommunications is not an option in quantum communication because of the no-cloning theorem. This problem could be overcome by implementing quantum repeater protocols, which create long-distance entanglement from shorter-distance entanglement via entanglement swapping. Such protocols require the capacity to create entanglement in a heralded fashion, to store it in quantum memories, and to swap it. One attractive general strategy for realizing quantum repeaters is based on the use of atomic ensembles as quantum memories, in combination with linear optical techniques and photon counting to perform all required operations. Here the theoretical and experimental status quo of this very active field are reviewed. The potentials of different approaches are compared quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons.

  9. Directly repeated sequences associated with pathogenic mitochondrial DNA deletions.

    PubMed Central

    Johns, D R; Rutledge, S L; Stine, O C; Hurko, O

    1989-01-01

    We determined the nucleotide sequences of junctional regions associated with large deletions of mitochondrial DNA found in four unrelated individuals with a phenotype of chronic progressive external ophthalmoplegia. In each patient, the deletion breakpoint occurred within a directly repeated sequence of 13-18 base pairs, present in different regions of the normal mitochondrial genome-separated by 4.5-7.7 kilobases. In two patients, the deletions were identical. When all four repeated sequences are compared, a consensus sequence of 11 nucleotides emerges, similar to putative recombination signals, suggesting the involvement of a recombinational event. Partially deleted and normal mitochondrial DNAs were found in all tissues examined, but in very different proportions, indicating that these mutations originated before the primary cell layers diverged. Images PMID:2813377

  10. Versatile communication strategies among tandem WW domain repeats.

    PubMed

    Dodson, Emma Joy; Fishbain-Yoskovitz, Vered; Rotem-Bamberger, Shahar; Schueler-Furman, Ora

    2015-03-01

    Interactions mediated by short linear motifs in proteins play major roles in regulation of cellular homeostasis since their transient nature allows for easy modulation. We are still far from a full understanding and appreciation of the complex regulation patterns that can be, and are, achieved by this type of interaction. The fact that many linear-motif-binding domains occur in tandem repeats in proteins indicates that their mutual communication is used extensively to obtain complex integration of information toward regulatory decisions. This review is an attempt to overview, and classify, different ways by which two and more tandem repeats cooperate in binding to their targets, in the well-characterized family of WW domains and their corresponding polyproline ligands.

  11. The first crystal structure of an archaeal helical repeat protein

    PubMed Central

    Yoneda, Kazunari; Sakuraba, Haruhiko; Tsuge, Hideaki; Katunuma, Nobuhiko; Kuramitsu, Seiki; Kawabata, Takeshi; Ohshima, Toshihisa

    2005-01-01

    The crystal structure of ST1625p, a protein encoded by a hypothetical open reading frame ST1625 in the genome of the hyperthermophilic archaeon Sulfolobus tokodaii, was determined at 2.2 Å resolution. The only sequence similarity exhibited by the amino-acid sequence of ST1625p was a 33% identity with the sequence of SSO0983p from S. solfataricus. The 19 kDa monomeric protein was observed to consist of a right-handed superhelix assembled from a tandem repeat of ten α-­helices. A structural homology search using the DALI and MATRAS algorithms indicates that this protein can be classified as a helical repeat protein. PMID:16511116

  12. A low-magnetic-field soft gamma repeater.

    PubMed

    Rea, N; Esposito, P; Turolla, R; Israel, G L; Zane, S; Stella, L; Mereghetti, S; Tiengo, A; Götz, D; Göğüş, E; Kouveliotou, C

    2010-11-12

    Soft gamma repeaters (SGRs) and anomalous x-ray pulsars form a rapidly increasing group of x-ray sources exhibiting sporadic emission of short bursts. They are believed to be magnetars, that is, neutron stars powered by extreme magnetic fields, B ~ 10(14) to 10(15) gauss. We report on a soft gamma repeater with low magnetic field, SGR 0418+5729, recently detected after it emitted bursts similar to those of magnetars. X-ray observations show that its dipolar magnetic field cannot be greater than 7.5 × 10(12) gauss, well in the range of ordinary radio pulsars, implying that a high surface dipolar magnetic field is not necessarily required for magnetar-like activity. The magnetar population may thus include objects with a wider range of B-field strengths, ages, and evolutionary stages than observed so far.

  13. Repeated Witnessing of Conspecifics in Pain: Effects on Emotional Contagion

    PubMed Central

    Bruls, Rune; Han, Yingying; Heinemans, Mirjam; Pruis, Ilanah; Gazzola, Valeria; Keysers, Christian

    2015-01-01

    Witnessing of conspecifics in pain has been shown to elicit socially triggered freezing in rodents. It is unknown how robust this response is to repeated exposure to a cage-mate experiencing painful stimulation. To address this question, shock-experienced Observer rats repeatedly witnessed familiar Demonstrators receive painful footshocks (six sessions). Results confirm that Observers freeze during the first testing session. The occurrence of this behaviour however gradually diminished as the experimental sessions progressed, reaching minimal freezing levels by the end of the experiments. In contrast, the appearance and continuous increase in the frequency of yawning, a behavior that was inhibited by metyrapone (i.e,. a glucocorticoid synthesis blocker), might represent an alternative coping strategy, suggesting that the observer’s reduced freezing does not necessarily indicate a disappearance in the affective response to the Demonstrator’s distress. PMID:26356506

  14. Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

    DTIC Science & Technology

    2014-09-01

    TCF7L2 fusion. Nat Genet 43, 964-968 (2011). 22. Jiang, J., Birchler, J.A., Parrott, W.A. & Dawe, R.K. A molecular view of plant centromeres. Trends...these highly specific and abundant transcripts as novel biomarkers for early detection. Keywords cancer genetics , satellite repeats, metastasis...goals of the project and we are planning to focus on two major questions based on our new findings. The modified aims are as follows for this

  15. Performance Tests for Repeated Measures: Moran and Computer Batteries.

    DTIC Science & Technology

    1981-11-01

    Alvah C. Bittner, Jr., Robert C. Carter, and Michele Krause November 1981 NAALBIDNAIC LBRAORG New rlens, ousono/Q - 4-. UNCLASSIFIED SECURITY...Robert C. Carter, and Michele Krause 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT. TASK AREA & WORK UNIT NUMBERS Naval...So 7it NBDL - 81R012 Performance Tests for Repeated Measures: Moran and Computer Batteries Alvah C. Bittner, Jr., Robert C. Carter, and Michele Krause

  16. Repeated snake bite for recreation: Mechanisms and implications

    PubMed Central

    Senthilkumaran, Subramanian; Shah, Sweni; Balamurugan, Namasivayam; Menezes, Ritesh G; Thirumalaikolundusubramanian, Ponniah

    2013-01-01

    Snake venom use for recreational purposes has been documented earlier. Willfully subjecting oneself to repeated lethal snake bite as a source of getting relieved of stress and recreation observed in two healthy software engineers, without any underlying psychiatric ailments or comorbidities along with probable mechanisms, are reported. Emergency physicians and practitioners have to be aware of novel methods of exposure to snake venom so as to recognize such cases and treat them accordingly. PMID:24404461

  17. Repeated wildfires alter forest recovery of mixed-conifer ecosystems.

    PubMed

    Stevens-Rumann, Camille; Morgan, Penelope

    2016-09-01

    Most models project warmer and drier climates that will contribute to larger and more frequent wildfires. However, it remains unknown how repeated wildfires alter post-fire successional patterns and forest structure. Here, we test the hypothesis that the number of wildfires, as well as the order and severity of wildfire events interact to alter forest structure and vegetation recovery and implications for vegetation management. In 2014, we examined forest structure, composition, and tree regeneration in stands that burned 1-18 yr before a subsequent 2007 wildfire. Three important findings emerged: (1) Repeatedly burned forests had 15% less woody surface fuels and 31% lower tree seedling densities compared with forests that only experienced one recent wildfire. These repeatedly burned areas are recovering differently than sites burned once, which may lead to alternative ecosystem structure. (2) Order of burn severity (high followed by low severity compared with low followed by high severity) did influence forest characteristics. When low burn severity followed high, forests had 60% lower canopy closure and total basal area with 92% fewer tree seedlings than when high burn severity followed low. (3) Time between fires had no effect on most variables measured following the second fire except large woody fuels, canopy closure and tree seedling density. We conclude that repeatedly burned areas meet many vegetation management objectives of reduced fuel loads and moderate tree seedling densities. These differences in forest structure, composition, and tree regeneration have implications not only for the trajectories of these forests, but may reduce fire intensity and burn severity of subsequent wildfires and may be used in conjunction with future fire suppression tactics.

  18. Tractography of the optic radiation: a repeatability and reproducibility study.

    PubMed

    Dayan, Michael; Kreutzer, Sylvia; Clark, Chris A

    2015-04-01

    Our main objective was to evaluate the repeatability and reproducibility of optic radiation (OR) reconstruction from diffusion MRI (dMRI) data. 14 adults were scanned twice with the same 60-direction dMRI sequence. Peaks in the diffusion profile were estimated with the single tensor (ST), Q-ball (QSH) and persistent angular structure (PAS) methods. Segmentation of the OR was performed by two experimenters with probabilistic tractography based on a manually drawn region-of-interest (ROI) protocol typically employed for OR segmentation, with both standard and extended sets of ROIs. The repeatability and reproducibility were assessed by calculating the intra-class correlation coefficient (ICC) of intra- and inter-rater experiments, respectively. ICCs were calculated for commonly used dMRI metrics (FA, MD, AD, RD) and anatomical dimensions of the optic radiation (distance from Meyer's loop to the temporal pole, ML-TP), as well as the Dice similarity coefficient (DSC) between the raters' OR segmentation. Bland-Altman plots were also calculated to investigate bias and variability in the reproducibility measurements. The OR was successfully reconstructed in all subjects by both raters. The ICC was found to be in the good to excellent range for both repeatability and reproducibility of the dMRI metrics, DSC and ML-TP distance. The Bland-Altman plots did not show any apparent systematic bias for any quantities. Overall, higher ICC values were found for the multi-fiber methods, QSH and PAS, and for the standard set of ROIs. Considering the good to excellent repeatability and reproducibility of all the quantities investigated, these findings support the use of multi-fiber OR reconstruction with a limited number of manually drawn ROIs in clinical applications utilizing either OR microstructure characterization or OR dimensions, as is the case in neurosurgical planning for temporal lobectomy.

  19. (Efficient identification and analysis of low and medium frequency repeats)

    SciTech Connect

    Jurka, J.

    1991-08-28

    The effective starting date of this grant was May 15. In the first three months of this project we focused primarily on organizational and technical aspects of our research which included: organization of the database of repeats in primates; preparation of software for rapid and sensitive search of novel repetitive elements in GenBank; purchase and installation of the Sun workstation; and research on the mammal-specific MAR1 family of repetitive elements (to be communicated in October).

  20. Hepcidin level predicts hemoglobin concentration in individuals undergoing repeated phlebotomy.

    PubMed

    Mast, Alan E; Schlumpf, Karen S; Wright, David J; Johnson, Bryce; Glynn, Simone A; Busch, Michael P; Olbina, Gordana; Westerman, Mark; Nemeth, Elizabeta; Ganz, Tomas

    2013-08-01

    Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology when repeated blood loss occurs has not been characterized. Hepcidin was assayed in plasma samples obtained from 114 first-time/reactivated (no blood donations in preceding 2 years) female donors and 34 frequent (≥3 red blood cell donations in preceding 12 months) male donors as they were phlebotomized ≥4 times over 18-24 months. Hepcidin levels were compared to ferritin and hemoglobin levels using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin levels declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin levels correlated well with each other (Spearman's correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (>45.7 ng/mL) or decreasing hepcidin and low ferritin (>26 ng/mL), and was essentially zero for other subjects including those with high (>45.7 ng/mL) or increasing hepcidin and low ferritin (>26 ng/mL) levels (P<0.001). In conclusion, hepcidin levels change rapidly in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of a low levels of ferritin suggests that plasma hepcidin concentration may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone. Clinicaltrials.gov identifier: NCT00097006.

  1. Analysis of Flow Angularity Repeatability Tests in the NTF

    NASA Technical Reports Server (NTRS)

    Hemsch, Michael J.

    2006-01-01

    An extensive data base of flow angularity repeatability measurements from four NTF check standard model tests is analyzed for statistical consistency and to characterize the results for prediction of angle-of-attack uncertainty for customer tests. A procedure for quality assurance for flow angularity measurements during customer tests is also presented. The efficacy of the procedure is tested using results from a customer test.

  2. Strategies to Improve Repeat Fecal Occult Blood Testing Cancer Screening

    PubMed Central

    Davis, Terry C.; Arnold, Connie L.; Bennett, Charles L.; Wolf, Michael S.; Reynolds, Cristalyn; Liu, Dachao; Rademaker, Alfred

    2013-01-01

    Background A comparative effectiveness intervention by this team improved initial fecal occult blood testing (FOBT) rates from 3% to 53% among community clinic patients. The purpose of this study was to evaluate the effectiveness and costs associated with a literacy-informed intervention on repeat FOBT testing. Methods Between 2008 and 2011, a three-arm quasi-experiential comparative effectiveness evaluation was conducted in 8 community clinics in Louisiana. Clinics were randomly assigned to receive: enhanced care, a screening recommendation and FOBT kit annually; a brief educational intervention where patients additionally received a literacy appropriate pamphlet and simplified FOBT instructions; or nurse support where a nurse manager provided the education and followed up with phone support. In year 2 all materials were mailed. The study consisted of 461 patients, ages 50–85, with a negative initial FOBT. Results Repeat FOBT rates were 38% enhanced care, 33% education, and 59% with nurse support (p=0.017). After adjusting for age, race, gender, and literacy, patients receiving nurse support were 1.46 times more likely to complete repeat FOBT screening than those receiving education (95% CI 1.14–1.06, p=0.002) and 1.45 times more likely than those in enhanced care but this was not significant (95% CI 0.93–2.26 p=0.10). The incremental cost per additional person screened was $2,450 for nurse over enhanced care. Conclusion A mailed pamphlet and FOBT with simplified instructions did not improve annual screening. Impact Telephone outreach by a nurse manager was effective in improving rates of repeat FOBT yet this may be too costly for community clinics. PMID:24192009

  3. Synthesis of Calocybe indica var. APK2 polysaccharide repeating unit.

    PubMed

    Zhang, Lei; Zhu, Xiangming

    2014-06-04

    The first total synthesis of p-methoxyphenyl α-l-fucopyranosyl-(1→6)-α-d-galactopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside (2) was achieved starting from five monosaccharide building blocks. This structure represents the repeating unit of the polysaccharide isolated from edible mushroom Calocybe indica var. APK2, and was synthesized in high overall yield via a convergent '3+2' glycosylation strategy.

  4. Short-Sequence DNA Repeats in Prokaryotic Genomes

    PubMed Central

    van Belkum, Alex; Scherer, Stewart; van Alphen, Loek; Verbrugh, Henri

    1998-01-01

    Short-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many prokaryotic genomes. These loci harbor short or long stretches of repeated nucleotide sequence motifs. DNA sequence motifs in a single locus can be identical and/or heterogeneous. SSRs are encountered in many different branches of the prokaryote kingdom. They are found in genes encoding products as diverse as microbial surface components recognizing adhesive matrix molecules and specific bacterial virulence factors such as lipopolysaccharide-modifying enzymes or adhesins. SSRs enable genetic and consequently phenotypic flexibility. SSRs function at various levels of gene expression regulation. Variations in the number of repeat units per locus or changes in the nature of the individual repeat sequences may result from recombination processes or polymerase inadequacy such as slipped-strand mispairing (SSM), either alone or in combination with DNA repair deficiencies. These rather complex phenomena can occur with relative ease, with SSM approaching a frequency of 10−4 per bacterial cell division and allowing high-frequency genetic switching. Bacteria use this random strategy to adapt their genetic repertoire in response to selective environmental pressure. SSR-mediated variation has important implications for bacterial pathogenesis and evolutionary fitness. Molecular analysis of changes in SSRs allows epidemiological studies on the spread of pathogenic bacteria. The occurrence, evolution and function of SSRs, and the molecular methods used to analyze them are discussed in the context of responsiveness to environmental factors, bacterial pathogenicity, epidemiology, and the availability of full-genome sequences for increasing numbers of microorganisms, especially those that are medically relevant. PMID:9618442

  5. Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins

    PubMed Central

    Hu, Yueming; Huang, He; Hui, Xinjie; Cheng, Xi; White, Aaron P.

    2016-01-01

    Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In Yersinia, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by Yersinia genomes or their evolution. In this study, the Yersinia LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 protein-encoding genes (LRR1 genes) varied dramatically and were categorized into 4 subgroups (a to d), with the LRR1a to -c genes evolving from the same ancestor and LRR1d genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of Yersinia. PMID:27217422

  6. Investigating repeatable ionospheric features during large space storms and superstorms

    DTIC Science & Technology

    2014-08-25

    Final 3. DATES COVERED (From - To) Mar-13 – Jan-14 4. TITLE AND SUBTITLE Investigating repeatable ionospheric features during large... Ionosphere -Plasmasphere Electrodynamics). The 6 April 2000 superstorm (Dst = -314 nT) was complex as the prompt penetration electric field developed and...event because of its unusual pattern producing unusual ionospheric storms. Our results reveal some strong longitudinal differences caused by the

  7. Entanglement over global distances via quantum repeaters with satellite links

    NASA Astrophysics Data System (ADS)

    Boone, K.; Bourgoin, J.-P.; Meyer-Scott, E.; Heshami, K.; Jennewein, T.; Simon, C.

    2015-05-01

    We study entanglement creation over global distances based on a quantum repeater architecture that uses low-Earth-orbit satellites equipped with entangled photon sources, as well as ground stations equipped with quantum nondemolition detectors and quantum memories. We show that this approach allows entanglement creation at viable rates over distances that are inaccessible via direct transmission through optical fibers or even from very distant satellites.

  8. Feasibility, Accuracy, and Repeatability of Suprathreshold Saccadic Vector Optokinetic Perimetry

    PubMed Central

    Murray, Ian C.; Cameron, Lorraine A.; McTrusty, Alice D.; Perperidis, Antonios; Brash, Harry M.; Fleck, Brian W.; Minns, Robert A.

    2016-01-01

    Purpose To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokinetic Perimetry (SVOP) by comparison with Humphrey Field Analyzer (HFA) perimetry. Methods The subjects included children with suspected field defects (n = 10, age 5–15 years), adults with field defects (n = 33, age 39–78 years), healthy children (n = 12, age 6–14 years), and healthy adults (n = 30, age 16–61 years). The test protocol comprised repeat suprathreshold SVOP and HFA testing with the C-40 test pattern. Feasibility was assessed by protocol completeness. Sensitivity, specificity, and accuracy of SVOP was established by comparison with reliable HFA tests in two ways: (1) visual field pattern results (normal/abnormal), and (2) individual test point outcomes (seen/unseen). Repeatability of each test type was assessed using Cohen's kappa coefficient. Results Of subjects, 82% completed a full protocol. Poor reliability of HFA testing in child patients limited the robustness of comparisons in this group. Sensitivity, specificity, and accuracy across all groups when analyzing the visual field pattern results was 90.9%, 88.5%, and 89.0%, respectively, and was 69.1%, 96.9%, and 95.0%, respectively, when analyzing the individual test points. Cohen's kappa coefficient for repeatability of SVOP and HFA was excellent (0.87 and 0.88, respectively) when assessing visual field pattern results, and substantial (0.62 and 0.74, respectively) when assessing test point outcomes. Conclusions SVOP was accurate in this group of adults. Further studies are required to assess SVOP in child patient groups. Translational Relevance SVOP technology is still in its infancy but is used in a number of centers. It will undergo iterative improvements and this study provides a benchmark for future iterations. PMID:27617181

  9. Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

    DTIC Science & Technology

    2015-11-01

    transcripts as novel biomarkers for early detection. 2. KEYWORDS cancer genetics , satellite repeats, metastasis, circulating tumor cell, pancreatic cancer...to formally evaluate effects on CTCs in the future using the pancreatic genetically engineered mouse model, which was outside the scope of this...bCenter for Biomedical Informatics, Harvard Medical School, Boston, MA 02115; cDivision of Genetics , Brigham and Women’s Hospital, Boston, MA 02115

  10. Repeatability of Feather Mite Prevalence and Intensity in Passerine Birds

    PubMed Central

    Diaz-Real, Javier; Serrano, David; Pérez-Tris, Javier; Fernández-González, Sofía; Bermejo, Ana; Calleja, Juan A.; De la Puente, Javier; De Palacio, Diana; Martínez, José L.; Moreno-Opo, Rubén; Ponce, Carlos; Frías, Óscar; Tella, José L.; Møller, Anders P.; Figuerola, Jordi; Pap, Péter L.; Kovács, István; Vágási, Csongor I.; Meléndez, Leandro; Blanco, Guillermo; Aguilera, Eduardo; Senar, Juan Carlos; Galván, Ismael; Atiénzar, Francisco; Barba, Emilio; Cantó, José L.; Cortés, Verónica; Monrós, Juan S.; Piculo, Rubén; Vögeli, Matthias; Borràs, Antoni; Navarro, Carlos; Mestre, Alexandre; Jovani, Roger

    2014-01-01

    Understanding why host species differ so much in symbiont loads and how this depends on ecological host and symbiont traits is a major issue in the ecology of symbiosis. A first step in this inquiry is to know whether observed differences among host species are species-specific traits or more related with host-symbiont environmental conditions. Here we analysed the repeatability (R) of the intensity and the prevalence of feather mites to partition within- and among-host species variance components. We compiled the largest dataset so far available: 119 Paleartic passerine bird species, 75,944 individual birds, ca. 1.8 million mites, seven countries, 23 study years. Several analyses and approaches were made to estimate R and adjusted repeatability (Radj) after controlling for potential confounding factors (breeding period, weather, habitat, spatial autocorrelation and researcher identity). The prevalence of feather mites was moderately repeatable (R = 0.26–0.53; Radj = 0.32–0.57); smaller values were found for intensity (R = 0.19–0.30; Radj = 0.18–0.30). These moderate repeatabilities show that prevalence and intensity of feather mites differ among species, but also that the high variation within species leads to considerable overlap among bird species. Differences in the prevalence and intensity of feather mites within bird species were small among habitats, suggesting that local factors are playing a secondary role. However, effects of local climatic conditions were partially observed for intensity. PMID:25216248

  11. Can Repeated Painful Blunt Impact Deter Approach Toward a Goal?

    DTIC Science & Technology

    2012-11-29

    NOV 2012 2. REPORT TYPE Conference Presentation 3. DATES COVERED 00-00-2008 to 00-00-2010 4. TITLE AND SUBTITLE Can Repeated Painful Blunt...SUPPLEMENTARY NOTES 14. ABSTRACT Painful blunt impact from a low-mass, high-speed projectile has been considered as a possible non-lethal weapon for...impacts produced varied pain ratings, but pain was not a predictive factor in any escape, avoidance, or performance measure. Subjects who chose not to

  12. Can Repeated Painful Blunt Impact Deter Approach Toward a Goal?

    DTIC Science & Technology

    2010-11-29

    1 CAN REPEATED PAINFUL BLUNT IMPACT DETER APPROACH TOWARD A GOAL? K. R. Short*, G. Reid, G. Cooke Target Behavioral Response Laboratory, US...Angeles, CA 90095 ABSTRACT Painful blunt impact from a low-mass, high-speed projectile has been considered as a possible non-lethal weapon for...accuracy. Blunt impacts produced varied pain ratings, but pain was not a predictive factor in any escape, avoidance, or performance measure. Subjects

  13. Evolution of Repeated Sequence Arrays in the D-Loop Region of Bat Mitochondrial DNA

    PubMed Central

    Wilkinson, G. S.; Mayer, F.; Kerth, G.; Petri, B.

    1997-01-01

    Analysis of mitochondrial DNA control region sequences from 41 species of bats representing 11 families revealed that repeated sequence arrays near the tRNA-Pro gene are present in all vespertilionine bats. Across 18 species tandem repeats varied in size from 78 to 85 bp and contained two to nine repeats. Heteroplasmy ranged from 15% to 63%. Fewer repeats among heteroplasmic than homoplasmic individuals in a species with up to nine repeats indicates selection may act against long arrays. A lower limit of two repeats and more repeats among heteroplasmic than homoplasmic individuals in two species with few repeats suggests length mutations are biased. Significant regressions of heteroplasmy, θ and π, on repeat number further suggest that repeat duplication rate increases with repeat number. Comparison of vespertilionine bat consensus repeats to mammal control region sequences revealed that tandem repeats of similar size, sequence and number also occur in shrews, cats and bighorn sheep. The presence of two conserved protein-binding sequences in all repeat units indicates that convergent evolution has occurred by duplication of functional units. We speculate that D-loop region tandem repeats may provide signal redundancy and a primitive repair mechanism in the event of somatic mutations to these binding sites. PMID:9215906

  14. Expansion and Function of Repeat Domain Proteins During Stress and Development in Plants

    PubMed Central

    Sharma, Manisha; Pandey, Girdhar K.

    2016-01-01

    The recurrent repeats having conserved stretches of amino acids exists across all domains of life. Subsequent repetition of single sequence motif and the number and length of the minimal repeating motifs are essential characteristics innate to these proteins. The proteins with tandem peptide repeats are essential for providing surface to mediate protein–protein interactions for fundamental biological functions. Plants are enriched in tandem repeat containing proteins typically distributed into various families. This has been assumed that the occurrence of multigene repeats families in plants enable them to cope up with adverse environmental conditions and allow them to rapidly acclimatize to these conditions. The evolution, structure, and function of repeat proteins have been studied in all kingdoms of life. The presence of repeat proteins is particularly profuse in multicellular organisms in comparison to prokaryotes. The precipitous expansion of repeat proteins in plants is presumed to be through internal tandem duplications. Several repeat protein gene families have been identified in plants. Such as Armadillo (ARM), Ankyrin (ANK), HEAT, Kelch-like repeats, Tetratricopeptide (TPR), Leucine rich repeats (LRR), WD40, and Pentatricopeptide repeats (PPR). The structure and functions of these repeat proteins have been extensively studied in plants suggesting a critical role of these repeating peptides in plant cell physiology, stress and development. In this review, we illustrate the structural, functional, and evolutionary prospects of prolific repeat proteins in plants. PMID:26793205

  15. In vivo analysis of human nucleoporin repeat domain interactions

    PubMed Central

    Xu, Songli; Powers, Maureen A.

    2013-01-01

    The nuclear pore complex (NPC), assembled from ∼30 proteins termed nucleoporins (Nups), mediates selective nucleocytoplasmic trafficking. A subset of nucleoporins bear a domain with multiple phenylalanine–glycine (FG) motifs. As binding sites for transport receptors, FG Nups are critical in translocation through the NPC. Certain FG Nups are believed to associate via low-affinity, cohesive interactions to form the permeability barrier of the pore, although the form and composition of this functional barrier are debated. We used green fluorescent protein–Nup98/HoxA9 constructs with various numbers of repeats and also substituted FG domains from other nucleoporins for the Nup98 domain to directly compare cohesive interactions in live cells by fluorescence recovery after photobleaching (FRAP). We find that cohesion is a function of both number and type of FG repeats. Glycine–leucine–FG (GLFG) repeat domains are the most cohesive. FG domains from several human nucleoporins showed no interactions in this assay; however, Nup214, with numerous VFG motifs, displayed measurable cohesion by FRAP. The cohesive nature of a human nucleoporin did not necessarily correlate with that of its yeast orthologue. The Nup98 GLFG domain also functions in pore targeting through binding to Nup93, positioning the GLFG domain in the center of the NPC and supporting a role for this nucleoporin in the permeability barrier. PMID:23427268

  16. Unusually large telomeric repeats in the yeast Candida albicans.

    PubMed Central

    McEachern, M J; Hicks, J B

    1993-01-01

    We have identified sequences at the telomeres of the yeast Candida albicans and have found that they are composed of tandem copies of a 23-bp sequence. Through the cloning of native telomeric ends and the characterization and cloning of a "healed" end, we demonstrate that these repeated sequences are sufficient to function as a telomere. All copies of the 23-bp repeat that have been sequenced from a number of C. albicans strains are identical. In contrast, adjacent subtelomeric sequences are variable both between strains and within the WO-1 strain. In the WO-1 strain, the lengths of the telomeres are dependent upon growth temperature and are substantially longer at higher temperatures. Telomere growth is accompanied by increases in the number of the 23-bp repeats present on the telomeric fragments. These results suggest that either telomerase-maintained telomeres can be more complex in structure than was previously imagined or that Candida telomeres are maintained via a telomerase-independent mechanism. Images PMID:8417351

  17. Embryonic stem cell models of CAG repeat disease.

    PubMed

    Lorincz, Matthew T

    2005-01-01

    Nine neurodegenerative disorders are caused by CAG/polyglutamine (polyQ) repeat expansions. The underlying molecular mechanisms responsible for disease specific neurodegeneration remain elusive. In vivo and in vitro models utilizing rodent tissues, immortalized human cell lines, and human post mortem samples have provided insight into disease mechanisms. Concern that cellular and molecular processes observed in these models may not faithfully reproduce human diseases or be useful to identify compounds of therapeutic utility has driven development of new disease models. In addition to their therapeutic potential, stem cells represent a renewable source of tissue that can be directed into neurons and glia and can be used to study neurodegenerative cascades from their inception. Neuronally differentiated human stem cells containing CAG repeat expansions have the potential to accurately replicate human CAG repeat diseases and may be a faithful predictor of which compounds will be of human benefit. As a first step in development of this type of model, we developed murine embryonic stem cell models to study the mechanisms of polyQ tract induced neuronal degeneration.

  18. Hippocampal ER stress and learning deficits following repeated pyrethroid exposure.

    PubMed

    Hossain, Muhammad M; DiCicco-Bloom, Emanuel; Richardson, Jason R

    2015-01-01

    Endoplasmic reticulum (ER) stress is implicated as a significant contributor to neurodegeneration and cognitive dysfunction. Previously, we reported that the widely used pyrethroid pesticide deltamethrin causes ER stress-mediated apoptosis in SK-N-AS neuroblastoma cells. Whether or not this occurs in vivo remains unknown. Here, we demonstrate that repeated deltamethrin exposure (3 mg/kg every 3 days for 60 days) causes hippocampal ER stress and learning deficits in adult mice. Repeated exposure to deltamethrin caused ER stress in the hippocampus as indicated by increased levels of C/EBP-homologous protein (131%) and glucose-regulated protein 78 (96%). This was accompanied by increased levels of caspase-12 (110%) and activated caspase-3 (50%). To determine whether these effects resulted in learning deficits, hippocampal-dependent learning was evaluated using the Morris water maze. Deltamethrin-treated animals exhibited profound deficits in the acquisition of learning. We also found that deltamethrin exposure resulted in decreased BrdU-positive cells (37%) in the dentate gyrus of the hippocampus, suggesting potential impairment of hippocampal neurogenesis. Collectively, these results demonstrate that repeated deltamethrin exposure leads to ER stress, apoptotic cell death in the hippocampus, and deficits in hippocampal precursor proliferation, which is associated with learning deficits.

  19. Efficacy of repeated psychophysiological detection of deception testing.

    PubMed

    Dollins, A B; Cestaro, V L; Pettit, D J

    1998-09-01

    Physiological measures were recorded during repeated psychophysiological detection of deception (PDD) tests to determine if reaction levels change with test repetition. Two groups of 22 healthy male subjects completed six peak of tension PDD tests on each of two test days. A minimum between test day interval of six days was maintained. The treatment group was programmed to respond deceptively to one of seven test questions while the control group was programmed to respond truthfully to all questions. The respiration and galvanic skin resistance (GSR) line lengths, GSR peak response amplitude and latency, and cardiovascular inter-beat-interval (IBI) were calculated for each response. Analyses indicated that, except for GSR peak response latency, differential physiological reactivity during a PDD test did not change significantly over repeated tests or days; there was a decrease in average respiration line lengths at the initial test(s) of each day; and differential changes in average respiration line length, GSR peak latency, and cardiovascular IBI responses corresponded to deception. Power analyses were calculated to assist in result interpretation. It is suggested that PDD decision accuracy, concerning subject veracity, should not decrease during repeated testing.

  20. Adeno-associated virus inverted terminal repeats stimulate gene editing.

    PubMed

    Hirsch, M L

    2015-02-01

    Advancements in genome editing have relied on technologies to specifically damage DNA which, in turn, stimulates DNA repair including homologous recombination (HR). As off-target concerns complicate the therapeutic translation of site-specific DNA endonucleases, an alternative strategy to stimulate gene editing based on fragile DNA was investigated. To do this, an episomal gene-editing reporter was generated by a disruptive insertion of the adeno-associated virus (AAV) inverted terminal repeat (ITR) into the egfp gene. Compared with a non-structured DNA control sequence, the ITR induced DNA damage as evidenced by increased gamma-H2AX and Mre11 foci formation. As local DNA damage stimulates HR, ITR-mediated gene editing was investigated using DNA oligonucleotides as repair substrates. The AAV ITR stimulated gene editing >1000-fold in a replication-independent manner and was not biased by the polarity of the repair oligonucleotide. Analysis of additional human DNA sequences demonstrated stimulation of gene editing to varying degrees. In particular, inverted yet not direct, Alu repeats induced gene editing, suggesting a role for DNA structure in the repair event. Collectively, the results demonstrate that inverted DNA repeats stimulate gene editing via double-strand break repair in an episomal context and allude to efficient gene editing of the human chromosome using fragile DNA sequences.

  1. CAG repeat expansions in bipolar and unipolar disorders

    SciTech Connect

    Oruc, L.; Verheyen, G.R.; Raeymaekers, P.; Van Broeckhoven, C.

    1997-03-01

    Family, twin, and adoption studies consistently have indicated that the familial aggregation of bipolar (BP) disorder and unipolar recurrent major depression (UPR) is accounted for largely by genetic factors. However, the mode of inheritance is complex. One of the possible explanations could be that a gene with variable penetrance and variable expression is involved. Recently there have been reports on a new class of genetic diseases caused by an abnormal trinucleotide-repeat expansion (TRE). In a number of genetic disorders, these dynamic mutations were proved to be the biological basis for the clinically observed phenomenon of anticipation. DNA consisting of repeated triplets of nucleotides becomes unstable and increases in size over generations within families, giving rise to an increased severity and/or an earlier onset of the disorder. It has been recognized for a long time that anticipation occurs in multiplex families transmitting mental illness. More recent studies also suggest that both BP disorder and UPR show features that are compatible with anticipation. Although the findings of anticipation in BP disorders and in UPR must be interpreted with caution because of the possible presence of numerous ascertainment biases, they support the hypothesis that pathological TREs are implicated in the transmission of these disorders. TRE combined with variable penetrance of expression could explain the complex transmission pattern observed in BP disorder. In view of this, the recent reports of an association between CAG-repeat length and BP disorder in a Belgian, Swedish, and British population are promising. 14 refs., 1 fig., 1 tab.

  2. Repeating tests: different roles in research studies and clinical medicine.

    PubMed

    Monach, Paul A

    2012-10-01

    Researchers often decide whether to average multiple results in order to produce more precise data, and clinicians often decide whether to repeat a laboratory test in order to confirm its validity or to follow a trend. Some of the major sources of variation in laboratory tests (analytical imprecision, within-subject biological variation and between-subject variation) and the effects of averaging multiple results from the same sample or from the same person over time are discussed quantitatively in this article. This analysis leads to the surprising conclusion that the strategy of averaging multiple results is only necessary and effective in a limited range of research studies. In clinical practice, it may be important to repeat a test in order to eliminate the possibility of a rare type of error that has nothing to do analytical imprecision or within-subject variation, and for this reason, paradoxically, it may be most important to repeat tests with the highest sensitivity and/or specificity (i.e., ones that are critical for clinical decision-making).

  3. The evolutionary origin of insect telomeric repeats, (TTAGG)n.

    PubMed

    Vítková, Magda; Král, Jirí; Traut, Walther; Zrzavý, Jan; Marec, Frantisek

    2005-01-01

    The (TTAGG)n sequence is supposed to be an ancestral DNA motif of telomeres in insects. Here we examined the occurrence of TTAGG telomeric repeats in other arthropods and their close relatives by Southern hybridization of genomic DNAs and fluorescence in-situ hybridization (FISH) of chromosomes with (TTAGG)n probes or, alternatively, with the 'vertebrate' telomeric probe, (TTAGGG)n. Our results show that the (TTAGG)n motif is conserved in entognathous hexapods (Diplura and Collembola), crustaceans (Malacostraca, Branchiura, Pentastomida, and Branchiopoda), myriapods (Diplopoda and Chilopoda), pycnogonids, and most chelicerates (Palpigradi, Amblypygi, Acari, Opiliones, Scorpiones, Pseudoscorpiones, and Solifugae) but not in spiders (Araneae). The presence of TTAGG repeats in these groups suggests that the sequence is an ancestral motif of telomeres not only in insects but in Arthropoda. We failed, however, to detect the TTAGG repeats in close relatives of the arthropods, Tardigrada and Onychophora. But while Onychophora had the 'vertebrate' (TTAGGG)n motif instead, the Tardigrada did not. The (TTAGG)n motif probably evolved from the (TTAGGG)n motif. Based on our and compiled data, we presume that the 'vertebrate' motif (TTAGGG)n is an ancestral motif of telomeres in bilaterian animals and possibly also in the superclade including animals, fungi and amoebozoans.

  4. Alu repeats as markers for forensic DNA analyses

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M.; Kass, D.H.

    1994-01-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 98.9% nucleotide identity with the HS subfamily consensus sequence, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 inch and 3 inch unique flanking DNA sequences from each HS Alu that allow the locus to be assayed for the presence or absence of the Alu repeat. The dimorphic HS Alu sequences probably inserted in the human genome after the radiation of modem humans (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project. HS Alu family member insertions differ from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) in that polymorphisms due to Alu insertions arise as a result of a unique event which has occurred only one time in the human population and spread through the population from that point. Therefore, individuals that share HS Alu repeats inherited these elements from a common ancestor. Most VNTR and RFLP polymorphisms may arise multiple times in parallel within a population.

  5. Repeat-containing protein effectors of plant-associated organisms

    PubMed Central

    Mesarich, Carl H.; Bowen, Joanna K.; Hamiaux, Cyril; Templeton, Matthew D.

    2015-01-01

    Many plant-associated organisms, including microbes, nematodes, and insects, deliver effector proteins into the apoplast, vascular tissue, or cell cytoplasm of their prospective hosts. These effectors function to promote colonization, typically by altering host physiology or by modulating host immune responses. The same effectors however, can also trigger host immunity in the presence of cognate host immune receptor proteins, and thus prevent colonization. To circumvent effector-triggered immunity, or to further enhance host colonization, plant-associated organisms often rely on adaptive effector evolution. In recent years, it has become increasingly apparent that several effectors of plant-associated organisms are repeat-containing proteins (RCPs) that carry tandem or non-tandem arrays of an amino acid sequence or structural motif. In this review, we highlight the diverse roles that these repeat domains play in RCP effector function. We also draw attention to the potential role of these repeat domains in adaptive evolution with regards to RCP effector function and the evasion of effector-triggered immunity. The aim of this review is to increase the profile of RCP effectors from plant-associated organisms. PMID:26557126

  6. Caffeine Ingestion Improves Repeated Freestyle Sprints in Elite Male Swimmers

    PubMed Central

    Goods, Paul S.R.; Landers, Grant; Fulton, Sacha

    2017-01-01

    The purpose of this investigation was to determine the efficacy of a moderate dose of caffeine to improve repeat-sprint performance in elite freestyle sprinters. Nine highly trained male swimmers performed 6 x 75 m freestyle sprints on two occasions 1-h after consuming either 3 mg·kg-1 caffeine (CAF), or placebo, in a cross-over manner. Capillary blood samples for the analysis of blood lactate concentration and pH were collected after the 1st, 3rd, and 5th sprint, while heart rate and perceived exertion (RPE) were collected after every sprint. There was a moderate effect for improved mean sprint time in the CAF condition (0.52 s; 1.3%; d = 0.50). When assessed individually, there was a large effect for improved performance in sprints 3 (1.00 s; 2.5%; d = 1.02) and 4 (0.84 s; 2.1%; d = 0.84) in CAF compared to placebo, with worthwhile performance improvement found for each of the first 5 sprints. There was a significant treatment effect for higher blood lactate concentration for CAF (p = 0.029), and a significant treatment*time effect for reduced pH in the CAF condition (p = 0.004). Mean heart rate (167 ± 9 bpm vs 169 ± 7 bpm) and RPE (17 ± 1 vs 17 ± 1) were not different between placebo and CAF trials, respectively. This investigation is the first to demonstrate enhanced repeat-sprint ability in swimmers following acute caffeine ingestion. It appears likely that the combination of a moderate dose of caffeine (3-6 mg·kg-1) with trained athletes is most likely to enhance repeat-sprint ability in various athletic populations; however, the exact mechanism(s) for an improved repeat-sprint ability following acute caffeine ingestion remain unknown. Key points A moderate dose of caffeine (3 mg·kg-1) ingested 1 h before a repeat-sprint freestyle set significantly improves mean sprint time in elite swimmers. The combination of at least a moderate dose of caffeine (>3 mg·kg-1) with trained athletes appears the most likely to result in ergogenic benefit to anaerobic

  7. Recombination frequency in plasmid DNA containing direct repeats--predictive correlation with repeat and intervening sequence length.

    PubMed

    Oliveira, Pedro H; Lemos, Francisco; Monteiro, Gabriel A; Prazeres, Duarte M F

    2008-09-01

    In this study, a simple non-linear mathematical function is proposed to accurately predict recombination frequencies in bacterial plasmid DNA harbouring directly repeated sequences. The mathematical function, which was developed on the basis of published data on deletion-formation in multicopy plasmids containing direct-repeats (14-856 bp) and intervening sequences (0-3872 bp), also accounts for the strain genotype in terms of its recA function. A bootstrap resampling technique was used to estimate confidence intervals for the correlation parameters. More than 92% of the predicted values were found to be within a pre-established +/-5-fold interval of deviation from experimental data. The correlation does not only provide a way to predict, with good accuracy, the recombination frequency, but also opens the way to improve insight into these processes.

  8. DNA motifs determining the accuracy of repeat duplication during CRISPR adaptation in Haloarcula hispanica

    PubMed Central

    Wang, Rui; Li, Ming; Gong, Luyao; Hu, Songnian; Xiang, Hua

    2016-01-01

    Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) acquire new spacers to generate adaptive immunity in prokaryotes. During spacer integration, the leader-preceded repeat is always accurately duplicated, leading to speculations of a repeat-length ruler. Here in Haloarcula hispanica, we demonstrate that the accurate duplication of its 30-bp repeat requires two conserved mid-repeat motifs, AACCC and GTGGG. The AACCC motif was essential and needed to be ∼10 bp downstream from the leader-repeat junction site, where duplication consistently started. Interestingly, repeat duplication terminated sequence-independently and usually with a specific distance from the GTGGG motif, which seemingly served as an anchor site for a molecular ruler. Accordingly, altering the spacing between the two motifs led to an aberrant duplication size (29, 31, 32 or 33 bp). We propose the adaptation complex may recognize these mid-repeat elements to enable measuring the repeat DNA for spacer integration. PMID:27085805

  9. GFP-based fluorescence assay for CAG repeat instability in cultured human cells.

    PubMed

    Santillan, Beatriz A; Moye, Christopher; Mittelman, David; Wilson, John H

    2014-01-01

    Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries.

  10. GFP-Based Fluorescence Assay for CAG Repeat Instability in Cultured Human Cells

    PubMed Central

    Santillan, Beatriz A.; Moye, Christopher; Mittelman, David; Wilson, John H.

    2014-01-01

    Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries. PMID:25423602

  11. Impaired sensorimotor gating in Fmr1 knock out and Fragile X premutation model mice.

    PubMed

    Renoux, A J; Sala-Hamrick, K J; Carducci, N M; Frazer, M; Halsey, K E; Sutton, M A; Dolan, D F; Murphy, G G; Todd, P K

    2014-07-01

    Fragile X syndrome (FXS) is a common inherited cause of intellectual disability that results from a CGG repeat expansion in the FMR1 gene. Large repeat expansions trigger both transcriptional and translational suppression of Fragile X protein (FMRP) production. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is an allelic neurodegenerative disease caused by smaller "pre-mutation" CGG repeat expansions that enhance FMR1 transcription but lead to translational inefficiency and reduced FMRP expression in animal models. Sensorimotor gating as measured by pre-pulse inhibition (PPI) is altered in both FXS patients and Fmr1 knock out (KO) mice. Similarly, FXTAS patients have demonstrated PPI deficits. Recent work suggests there may be overlapping synaptic defects between Fmr1 KO and CGG knock-in premutation mouse models (CGG KI). We therefore sought to interrogate PPI in CGG KI mice. Using a quiet PPI protocol more akin to human testing conditions, we find that Fmr1 KO animals have significantly impaired PPI. Using this same protocol, we find CGG KI mice demonstrate an age-dependent impairment in PPI compared to wild type (WT) controls. This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms.

  12. Site and Orbit Repeatabilities using Adaptive Mapping Functions

    NASA Astrophysics Data System (ADS)

    Desjardins, Camille; Gegout, Pascal; Soudarin, Laurent; Biancale, Richard; Perosanz, Felix

    2015-04-01

    The electromagnetic signals emitted by the satellite positioning systems travel at the speed of light in a straight line in a vacuum but are modified in their propagation through the neutral atmosphere by temporal and spatial changes of density, and composition and refractivity. These waves are slowed down and their trajectories are bent. This presentation summarizes the performances of the modeling of the tropospheric propagation by the ray tracing technique through the assimilations of the European Meteorological Centre (ECMWF) in the framework of realizing the geodetic reference frame. This goal is achieved by modeling the spatial variability of the propagation using the time variable three-dimensional physical parameters of the atmosphere. The tropospheric delays obtained by ray tracing in all directions throughout the meteorological model surrounding the geodetic site, are fitted by Adaptive Mapping Functions (AMF) parameterized by several tens of coefficients. The delays produced by the Horizon software are then experimented, kept unchanged or adjusted, when recovering a reference frame based on hundred sites using the GINS software. Without any adjustments of the tropospheric modeling, the subcentimetric performances of the AMF are demonstrated by the repeatability of sites positions and GPS satellites orbits. When some AMF coefficients are adjusted, the accuracy of orbits recovery in term of quadratic mean is 7 to 8 millimeters. This limit is imposed by the lack or deficiency of other models, such as non-tidal and tidal loading respectively. Hence the repeatability of the vertical position is not enhanced by changing the propagation model. At the contrary, the repeatability of the horizontal position of geodetic sites is greatly enhanced by accounting for the azimuthal variability provided by the realistic 3D shapes of the Atmosphere and the Earth and the rigorous interpolations of atmospheric parameters included in Adaptive Mapping Functions with respect

  13. IMHEX fuel cell repeat component manufacturing continuous improvement accomplishments

    SciTech Connect

    Jakaitis, L.A.; Petraglia, V.J.; Bryson, E.S.

    1996-12-31

    M-C Power is taking a power generation technology that has been proven in the laboratory and is making it a commercially competitive product. There are many areas in which this technology required scale up and refinement to reach the market entry goals for the IMHEX{reg_sign} molten carbonate fuel cell power plant. One of the primary areas that needed to be addressed was the manufacturing of the fuel cell stack. Up to this point, the fuel cell stack and associated components were virtually hand made for each system to be tested. M-C Power has now continuously manufactured the repeat components for three 250 kW stacks. M-C Power`s manufacturing strategy integrated both evolutionary and revolutionary improvements into its comprehensive commercialization effort. M-C Power`s objectives were to analyze and continuously improve stack component manufacturing and assembly techniques consistent with established specifications and commercial scale production requirements. Evolutionary improvements are those which naturally occur as the production rates are increased and experience is gained. Examples of evolutionary (learning curve) improvements included reducing scrap rates and decreasing raw material costs by buying in large quantities. Revolutionary improvements result in significant design and process changes to meet cost and performance requirements of the market entry system. Revolutionary changes often involve identifying new methods and developing designs to accommodate the new process. Based upon our accomplishments, M-C Power was able to reduce the cost of continuously manufactured fuel cell repeat components from the first to third 250 kW stack by 63%. This paper documents the continuous improvement accomplishments realized by M-C Power during IMHEX{reg_sign} fuel cell repeat component manufacturing.

  14. Evolution of Determinant Factors of Repeated Sprint Ability.

    PubMed

    Pareja-Blanco, Fernando; Suarez-Arrones, Luis; Rodríguez-Rosell, David; López-Segovia, Manuel; Jiménez-Reyes, Pedro; Bachero-Mena, Beatriz; González-Badillo, Juan José

    2016-12-01

    The aim of this study was to investigate the changes in the relationships between repeated sprint ability (RSA) and anthropometric measures as well as fitness qualities in soccer players. Twenty-one professional soccer players performed several anthropometric and physical tests including countermovement vertical jumps (CMJs), a straight-line 30 m sprint (T30), an RSA test (6 x 20 + 20 m with 20 s recovery), a progressive isoinertial loading test in a full squat, a Yo-Yo Intermittent Recovery Test Level-1 (YYIRT-1) and a 20 m shuttle run test (20mSRT). The mean (RSAmean), the fastest (RSAbest), each single sprint time, and the percentage in a sprint decrease (%Dec) in the RSA test were calculated. RSAbest correlated significantly with RSAmean (r = .82) and with all single sprints (p < 0.05), showing a downward trend as the number of sprints performed increased. No significant relationship was observed between the %Dec and RSA performance. CMJs and the T30 also showed a correlation with RSA performance, whereas lower limb strength did not show any relationship with RSA performance. RSAmean showed significant (p < 0.05) relationships with body mass (r = .44), adiposity (r = .59) and the YYIRT-1 (r = -.62), increasing as the number of repeated sprints increased. The 20mSRT showed minimal relationships with RSA performance. In conclusion, maximal sprint capacity seems to be relevant for the RSA performance, mainly in the first sprints. However, high intermittent endurance capacity and low adiposity might help enhance the RSA performance when increasing the number of repeated sprints.

  15. Neck-cooling improves repeated sprint performance in the heat

    PubMed Central

    Sunderland, Caroline; Stevens, Ryan; Everson, Bethan; Tyler, Christopher J.

    2015-01-01

    The present study evaluated the effect of neck-cooling during exercise on repeated sprint ability in a hot environment. Seven team-sport playing males completed two experimental trials involving repeated sprint exercise (5 × 6 s) before and after two 45 min bouts of a football specific intermittent treadmill protocol in the heat (33.0 ± 0.2°C; 53 ± 2% relative humidity). Participants wore a neck-cooling collar in one of the trials (CC). Mean power output and peak power output declined over time in both trials but were higher in CC (540 ± 99 v 507 ± 122 W, d = 0.32; 719 ± 158 v 680 ± 182 W, d = 0.24 respectively). The improved power output was particularly pronounced (d = 0.51–0.88) after the 2nd 45 min bout but the CC had no effect on % fatigue. The collar lowered neck temperature and the thermal sensation of the neck (P < 0.001) but had no effect on heart rate, fluid loss, fluid consumption, lactate, glucose, plasma volume change, cortisol, or thermal sensation (P > 0.05). There were no trial differences but interaction effects were demonstrated for prolactin concentration and rating of perceived exertion (RPE). Prolactin concentration was initially higher in the collar cold trial and then was lower from 45 min onwards (interaction trial × time P = 0.04). RPE was lower during the football intermittent treadmill protocol in the collar cold trial (interaction trial × time P = 0.01). Neck-cooling during exercise improves repeated sprint performance in a hot environment without altering physiological or neuroendocrinological responses. RPE is reduced and may partially explain the performance improvement. PMID:26594177

  16. Hyperventilation as a strategy for improved repeated sprint performance.

    PubMed

    Sakamoto, Akihiro; Naito, Hisashi; Chow, Chin-Moi

    2014-04-01

    Repeated high-intensity sprints incur substantial anaerobic metabolic challenges and create an acidic muscle milieu that is unfavorable for subsequent performance. Hyperventilation, resulting in respiratory alkalosis, acts as a compensatory mechanism for metabolic acidosis. This study tested the hypothesis that hyperventilation performed during recovery intervals would attenuate performance decrement in repeated sprint pedaling. Thirteen male university athletes performed 10 sets of 10-second maximal pedaling on a cycle ergometer with a 60-second recovery between sets under control (spontaneous breathing) and hyperventilation conditions in a crossover counter-balanced manner. Pedaling load was set at 0.075 × body mass. Peak and mean power outputs were documented for each set to compare performance decrements for 10 sets between conditions. Hyperventilation (60 breaths per minute and end-tidal partial pressure of CO2 maintained at 20-25 mm Hg) was performed 30 seconds before each sprint set. This intervention successfully increased blood pH by 0.03-0.07 but lowered P(CO2) by 1.2-8.4 mm Hg throughout exercise (p < 0.001). The peak and mean power outputs, and blood [La] accumulation were not significantly different between the conditions. However, a significant condition × time interaction existed for peak power (p = 0.035) and mean power (p = 0.023), demonstrating an attenuation in power decrement in later sprint sets with hyperventilation. In conclusion, hyperventilation implemented during recovery intervals of repeated sprint pedaling attenuated performance decrements in later exercise bouts that was associated with substantial metabolic acidosis. The practical implication is that hyperventilation may have a strategic role for enhancing training effectiveness and may give an edge in performance outcomes.

  17. Transient CNS responses to repeated binge ethanol treatment

    PubMed Central

    Zahr, Natalie M; Rohlfing, Torsten; Mayer, Dirk; Luong, Richard; Sullivan, Edith V; Pfefferbaum, Adolf

    2016-01-01

    Adaptive changes occur in response to repeated exposure to drugs. Although ethanol (EtOH) is known to induce pharmacokinetic tolerance, the effects of EtOH on in vivo, magnetic resonance (MR)-detectable brain measures across repeated exposures have not previously been reported. Of 28 rats weighing 341±22g at baseline, 15 were assigned to the EtOH group and 13 to the control (Ctrl) group. EtOH animals were exposed to 5 cycles of 4-days of EtOH treatment followed by 10 days of recovery. Rats in both groups had structural MR imaging (MRI) scans and whole brain MR spectroscopy (MRS) at baseline, immediately following each binge period, and after each recovery period (total=11 MR scans per rat). Average blood alcohol levels (BALs) across each of the 5, 4-day binge periods were 298, 300, 301, 312, 318 mg/dL. Cerebrospinal fluid (CSF) volumes of the lateral ventricles and cisterns showed enlargement with each binge EtOH exposure but recovery with each abstinence period. Similarly, changes to MRS metabolites were transient: levels of N-acetyl aspartate (NAA) and total creatine (tCr) decreased, while those of choline-containing compounds (Cho) and glutamate/glutamine (Glx) increased with each binge EtOH exposure cycle, but also recovered during each abstinence period. The directionality of changes in response to EtOH were in expected directions based on previous, single-binge EtOH exposure experiments, but the current results do not provide support for accruing pathology with repeated binge EtOH exposure. PMID:26283309

  18. Neck-cooling improves repeated sprint performance in the heat.

    PubMed

    Sunderland, Caroline; Stevens, Ryan; Everson, Bethan; Tyler, Christopher J

    2015-01-01

    The present study evaluated the effect of neck-cooling during exercise on repeated sprint ability in a hot environment. Seven team-sport playing males completed two experimental trials involving repeated sprint exercise (5 × 6 s) before and after two 45 min bouts of a football specific intermittent treadmill protocol in the heat (33.0 ± 0.2°C; 53 ± 2% relative humidity). Participants wore a neck-cooling collar in one of the trials (CC). Mean power output and peak power output declined over time in both trials but were higher in CC (540 ± 99 v 507 ± 122 W, d = 0.32; 719 ± 158 v 680 ± 182 W, d = 0.24 respectively). The improved power output was particularly pronounced (d = 0.51-0.88) after the 2nd 45 min bout but the CC had no effect on % fatigue. The collar lowered neck temperature and the thermal sensation of the neck (P < 0.001) but had no effect on heart rate, fluid loss, fluid consumption, lactate, glucose, plasma volume change, cortisol, or thermal sensation (P > 0.05). There were no trial differences but interaction effects were demonstrated for prolactin concentration and rating of perceived exertion (RPE). Prolactin concentration was initially higher in the collar cold trial and then was lower from 45 min onwards (interaction trial × time P = 0.04). RPE was lower during the football intermittent treadmill protocol in the collar cold trial (interaction trial × time P = 0.01). Neck-cooling during exercise improves repeated sprint performance in a hot environment without altering physiological or neuroendocrinological responses. RPE is reduced and may partially explain the performance improvement.

  19. Texting Adolescents in Repeat DKA and Their Caregivers

    PubMed Central

    Wagner, David V.; Barry, Samantha; Teplitsky, Lena; Sheffield, Annan; Stoeckel, Maggie; Ogden, Jimmie D.; Karkula, Elizabeth; Hartman, Alexandra; Duke, Danny C.; Spiro, Kim; Harris, Michael A.

    2016-01-01

    Background: Text message interventions are feasible, preferable, and sometimes effective for youth with diabetes. However, few, if any studies, have examined the personalized use of text messages with youth repeatedly hospitalized for diabetic ketoacidosis (DKA) and their caregivers. This study characterizes the use of personalized text messages in Novel Interventions in Children’s Healthcare (NICH). Methods: Approximately 2 months of text messages sent to youth with repeat DKA and their caregivers were logged regarding the following text characteristics: (1) content, (2) intervention type, (3) timing, and (4) recipient characteristics. Results: NICH interventionists sent 2.3 and 1.5 texts per day to patients and caregivers, respectively. Approximately 59% of outgoing texts occurred outside of typical business hours, and roughly 68% of texts contained some form of support and/or encouragement. The relation between type of intended intervention and day/time of text was significant, χ2(2, N = 5,808) = 266.93, P < .001. Interventionists were more likely to send behavioral intervention text messages outside of business hours, whereas they were more likely to send care coordination and case management text messages during business hours. Conclusions: To our knowledge, this is the first study to specifically categorize and describe the personalized use of text messages with youth repeatedly hospitalized for DKA and their caregivers. Findings indicate that a promising treatment program for these youth frequently used text interventions to deliver praise and encouragement to patients and caregivers alike, often outside of typical business hours, and tailored text content based on patient and caregiver characteristics. PMID:27030051

  20. Unnecessary repeated total cholesterol tests in biochemistry laboratory

    PubMed Central

    Demir, Suleyman; Zorbozan, Nergiz; Basak, Elif

    2016-01-01

    Introduction We aimed to determine the number of repeated cholesterol (RC) tests and the ratio of unnecessary-repeated cholesterol (URC) tests among patients admitted to Pamukkale University Hospital (Denizli, Turkey) and provide solutions to avoid URC testing. Materials and methods Total cholesterol (T-cholesterol) tests (N = 86,817) between June 2014 and May 2015 were evaluated. The tests performed more than once per patient were determined as RC test (N = 28,811). RC test with an interval shorter than 4 weeks were determined as URC test (N = 3968) according to the shortest retest interval stated in ACC/AHA blood cholesterol guideline. RC testing included internal medicine, surgery and paediatric outpatients and inpatients. Reference change value (RCV) of total cholesterol was calculated. Results The 33.1% of the T-cholesterol tests were RC tests (N = 28,811), 13.7% of them were URC tests (N = 3968). Our RCV value was 25%. The percentage change between consecutive tests was less than RCV in 86.1% (N = 3418) of URC tests. URC tests were performed more frequently in patients with desirable total cholesterol value (P < 0.001). Conclusion There is a significant part of repeated T-cholesterol tests requested in our hospital. URC test requests can be evaluated by laboratories and the obtained data should be shared with clinicians. Laboratories can calculate RCV for the tests they performed and report this value with the test result. To prevent from URC tests, a warning plug-in can be added to hospital information software in accordance with guidelines to prevent from URC test requests. PMID:26981021

  1. A MACROMOLECULAR REPEATING UNIT OF MITOCHONDRIAL STRUCTURE AND FUNCTION

    PubMed Central

    Fernández-Morán, H.; Oda, T.; Blair, P. V.; Green, D. E.

    1964-01-01

    A repeating particle associated with the cristae and the inner membrane of the external envelope has been recognized and characterized in beef heart mitochondria by correlated electron microscopic and biochemical studies. Many thousands (ca. 104 to 105) of these particles, disposed in regular arrays, are present in a single mitochondrion. The repeating particle, called the elementary particle (EP), consists of three parts: (1) a spherical or polyhedral head piece (80 to 100 A in diameter); (2) a cylindrical stalk (about 50 A long and 30 to 40 A wide); and (3) a base piece (40 x 110 A). The base pieces of the elementary particles form an integral part of the outer dense layers of the cristae. The elementary particles can be seen in electron micrographs of mitochondria in situ, of isolated mitochondria, and of submitochondrial particles with a complete electron transfer chain. Negative staining with phosphotungstate is only one of several techniques that can be used for reproducible demonstration of the repeating particles and underlying subunit organization of mitochondrial membranes. A particulate unit containing a complete electron transfer chain can be isolated from beef heart mitochondria. The isolated unit approximates in size that of the elementary particle in situ. The molecular weight of the particle in situ is calculated to be 1.3 x 106. Evidence is presented for identifying the isolated unit with the elementary particle visualized in situ. The elementary particle of the mitochondrion is believed to be a prototype of a class of functional particles or macromolecular assemblies of similar size found in association with membranes generally. PMID:14195622

  2. Repeated dose pharmacokinetics of pancopride in human volunteers.

    PubMed

    Salva, P; Costa, J; Pérez-Campos, A; Martínez-Tobed, A

    1994-11-01

    The aim of this study was to assess the pharmacokinetic profile of pancopride after repeated oral dose administration of 20 mg pancopride in tablet form once a day for 5 d in 12 healthy male volunteers. Plasma levels were measured by HPLC using a solid phase extraction method and automated injection. The minimum quantification limit of pancopride in plasma was 2 ng mL-1. The maximum plasma concentration (mean +/- SD) after the first dose was 92.5 +/- 41.5 ng ML-1 and tmax was 1.7 +/- 0.9 h. The elimination half-life (t1/2) was 14.3 +/- 6.9 h. The area under the concentration-time curve from zero to infinity (AUC) was 997 +/- 396 ng h mL-1. The maximum plasma concentration (mean +/- SD) at steady state (day 5) was 101.8 +/- 36.9 ng mL-1 and tmax was 2.2 +/- 1.2 h. The elimination half-life (t1/2) was 16.3 +/- 2.7 h and the minimum plasma concentration (Cssmin) was 16.6 +/- 6.9 ng mL-1. The area under the concentration-time curve during the dosing interval (AUCss tau) was 995 +/- 389 ng h mL-1. The average plasma concentration at steady state (Cssav) was 43.3 +/- 16.1 ng mL-1 and the experimental accumulation ratio (RAUC) was 1.34 +/- 0.19, whereas the mean theoretical value (R) was 1.40 +/- 0.29. The results obtained showed a good correlation between the experimental plasma levels and the expected values calculated using a repeated dose two-compartment model assessed by means of the Akaike value. It is concluded that the pharmacokinetics of pancopride are not modified after repeated dose administration.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Repeating Earthquakes on the Queen Charlotte Plate Boundary

    NASA Astrophysics Data System (ADS)

    Hayward, T. W.; Bostock, M. G.

    2015-12-01

    The Queen Charlotte Fault (QCF) is a major plate boundary located off the northwest coast of North America that has produced large earthquakes in 1949 (M8.1) and more recently in October, 2012 (M7.8). The 2012 event was dominated by thrusting despite the fact that plate motions at the boundary are nearly transcurrent. It is now widely believed that the plate boundary comprises the QCF (i.e., a dextral strike-slip fault) as well as an element of subduction of the Pacific Plate beneath the North American Plate. Repeating earthquakes and seismic tremor have been observed in the vicinity of the QCF; providing insight into the spatial and temporal characteristics of repeating earthquakes is the goal of this research. Due to poor station coverage and data quality, traditional methods of locating earthquakes are not applicable to these events. Instead, we have implemented an algorithm to locate local (i.e., < 100 km distance to epicenter) earthquakes using a single, three-component seismogram. This algorithm relies on the P-wave polarization and, through comparison with larger local events in the Geological Survey of Canada catalogue, is shown to yield epicentral locations accurate to within 5-10 km. A total of 24 unique families of repeating earthquakes has been identified, and 4 of these families have been located with high confidence. Their epicenters locate directly on the trace of the QCF and their depths are shallow (i.e., 5-15 km), consistent with the proposed depth of the QCF. Analysis of temporal recurrence leading up to the 2012 M7.8 event reveals a non-random pattern, with an approximately 15 day periodicity. Further analysis is planned to study whether this behaviour persists after the 2012 event and to gain insight into the effects of the 2012 event on the stress field and frictional properties of the plate boundary.

  4. Alu repeats as markers for human population genetics

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M.; Bazan, H.

    1993-09-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

  5. Evolution of Determinant Factors of Repeated Sprint Ability

    PubMed Central

    Suarez-Arrones, Luis; Rodríguez-Rosell, David; López-Segovia, Manuel; Jiménez-Reyes, Pedro; Bachero-Mena, Beatriz; González-Badillo, Juan José

    2016-01-01

    Abstract The aim of this study was to investigate the changes in the relationships between repeated sprint ability (RSA) and anthropometric measures as well as fitness qualities in soccer players. Twenty-one professional soccer players performed several anthropometric and physical tests including countermovement vertical jumps (CMJs), a straight-line 30 m sprint (T30), an RSA test (6 x 20 + 20 m with 20 s recovery), a progressive isoinertial loading test in a full squat, a Yo-Yo Intermittent Recovery Test Level-1 (YYIRT-1) and a 20 m shuttle run test (20mSRT). The mean (RSAmean), the fastest (RSAbest), each single sprint time, and the percentage in a sprint decrease (%Dec) in the RSA test were calculated. RSAbest correlated significantly with RSAmean (r = .82) and with all single sprints (p < 0.05), showing a downward trend as the number of sprints performed increased. No significant relationship was observed between the %Dec and RSA performance. CMJs and the T30 also showed a correlation with RSA performance, whereas lower limb strength did not show any relationship with RSA performance. RSAmean showed significant (p < 0.05) relationships with body mass (r = .44), adiposity (r = .59) and the YYIRT-1 (r = -.62), increasing as the number of repeated sprints increased. The 20mSRT showed minimal relationships with RSA performance. In conclusion, maximal sprint capacity seems to be relevant for the RSA performance, mainly in the first sprints. However, high intermittent endurance capacity and low adiposity might help enhance the RSA performance when increasing the number of repeated sprints. PMID:28031763

  6. Relationship between brief and prolonged repeated sprint ability.

    PubMed

    Oliver, Jonathan L; Armstrong, Neil; Williams, Craig A

    2009-01-01

    Repeated sprint ability (RSA) is often assessed over a brief time period with limited recovery between sprints; however, it is not known how performance in such tests is related to the ability to perform repeated sprints over a more prolonged duration. Eighteen boys aged 15.3+/-0.5 years completed both a brief and prolonged RSA test on a non-motorised treadmill. The brief RSA test consisted of seven 5s sprints with 20s of recovery between sprints and the prolonged RSA test lasted for 42min and included a 5s sprint every 2min. There was a moderate but significant relationship between the mean speed in both tests (r=0.51, p<0.05). The maximal speed achieved in a single sprint provided strong relationships with both brief RSA speed (r> or =0.72, p<0.001) and prolonged RSA speed (r> or =0.77, p<0.001). Total work done during the brief protocol was significantly correlated to both total work (r=0.81, p<0.001) and total sprint distance (r=0.79, p<0.001) during the prolonged test. There were no significant relationships between percentage decrement scores across the two protocols (r< or =0.33, p>0.05). Maximal speed in a single sprint and total work done during repeated sprints represent general qualities related to RSA that are independent of the test protocol. The mean speed and decrements in performance represent specific RSA qualities, which are dependent on the frequency of sprints and duration of the test protocol.

  7. Enhanced appetitive conditioning following repeated pretreatment with d-amphetamine.

    PubMed

    Harmer, C J; Phillips, G D

    1998-07-01

    The behavioural response to psychomotor stimulants is augmented with repeated exposure to these drugs. Enhanced stimulated dopamine overflow within the nucleus accumbens and amygdala has been found to accompany this behavioural sensitization. In the present experiment, rats received 2 mg/kg d-amphetamine or 1 ml/kg physiological saline once per day for 5 days. Five days later, a behavioural assay confirmed that prior repeated d-amphetamine treatment markedly enhanced the locomotor activating effects of a d-amphetamine (0.5 mg/kg, i.p.) challenge. Training on a Pavlovian conditioning task began six days subsequently. In Stage 1, a stimulus (light or tone, S-) was presented negatively correlated with a sucrose reward. In Stage 2, presentation of the alternative counterbalanced stimulus (light or tone, S+) was paired with the availability of a 10% sucrose solution. There were no differences between the two groups in their response to the the S- stimulus. However, sensitized animals showed a selective enhancement in the acquisition of conditioned responding to S+, relative to vehicle-injected controls. No differences in behaviour were recorded during the prestimulus periods, nor during presentations of sucrose. Levels of activity within the operant chamber extraneous to alcove approach were also similar in both groups of animals. The conditioned instrumental efficacy of S+, relative to S- was assessed in Stage 3, in which stimulus availability was made contingent on a novel lever-pressing response. Both groups showed a similar preference for the S+ over the S- stimulus. Hence, rats sensitized by prior repeated d-amphetamine showed enhanced appetitive Pavlovian conditioning, without subsequent effect on conditioned reward efficacy. These data are discussed in light of possible changes in mesoamygdaloid dopamine functioning.

  8. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress

    PubMed Central

    Brocherie, Franck; Morin, Jean-Benoit; Racinais, Sébastien; Millet, Grégoire P.; Périard, Julien D.

    2017-01-01

    Purpose Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C) and CON (25°C) conditions. Methods Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting. Results Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001) and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05) temperatures, together with thermal comfort (P<0.001) were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001) and contact time (+3.2±2.4%; P<0.01) higher in HOT for the mean of sets 1–3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001), with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06). Mean vertical (-2.6±5.5%; P<0.01), horizontal (-9.1±4.4%; P<0.001) and resultant ground reaction forces (-3.0±2.8%; P<0.01) along with vertical stiffness (-12.9±2.3%; P<0.001) and leg stiffness (-8.4±2.7%; P<0.01) decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001), with lower propulsive power values in set 2 (-6.6%; P<0.05) in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise. Conclusions Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations. PMID:28146582

  9. Characteristics of cloned repeated DNA sequences in the barley genome

    SciTech Connect

    Anan'ev, E.V.; Bochkanov, S.S.; Ryzhik, M.V.; Sonina, N.V.; Chernyshev, A.I.; Shchipkova, N.I.; Yakovleva, E.Yu.

    1986-12-01

    A partial clone library of barley DNA fragments based on plasmid pBR325 was created. The cloned EcoRI-fragments of chromosomal DNA are from 2 to 14 kbp in length. More than 95% of the barley DNA inserts comprise repeated sequences of different complexity and copy number. Certain of these DNA sequences are from families comprising at least 1% of the barley genome. A significant proportion of the clones hybridize with numerous sets of restriction fragments of genome DNA and they are dispersed throughout the barley chromosomes.

  10. Irregular Repeat-Accumulate Codes for Volume Holographic Memory Systems

    NASA Astrophysics Data System (ADS)

    Pishro-Nik, Hossein; Fekri, Faramarz

    2004-09-01

    We investigate the application of irregular repeat-accumulate (IRA) codes in volume holographic memory (VHM) systems. We introduce methodologies to design efficient IRA codes. We show that a judiciously designed IRA code for a typical VHM can be as good as the optimized irregular low-density-parity-check codes while having the additional advantage of lower encoding complexity. Moreover, we present a method to reduce the error-floor effect of the IRA codes in the VHM systems. This method explores the structure of the noise pattern in holographic memories. Finally, we explain why IRA codes are good candidates for the VHM systems.

  11. [Changes in mesenteric microcirculation in rats following repeated skin burns].

    PubMed

    Shtykhno, Iu M

    1976-07-01

    Acute experiments were conducted on rats; repeated extensive burn of a convalescent who formerly sustained the burn disease was better tolerated, led tono fatal outcome and was accompanied by moderate microcirculatory disturbances. The smae burn was accompanied in intact rats by a severe shock followed by death, intravascular aggregation of erythrocytes and significant microcirculatory disturbances leading to disturbance of tissue nutrition. It is supposed that the results obtained could serve as an indirect proof that toxemia played an important role in the genesis of intravascular aggregation of erythrocytes in burn shock.

  12. Visualizing sediment dynamics through repeated high-resolution multibeam mapping

    NASA Astrophysics Data System (ADS)

    de Vries, J. J.; Greinert, J.; Maierhofer, T.

    2013-12-01

    Multibeam mapping has become a common method for mapping the seafloor in shallow and great water depths with different spatial resolutions depending on the system platform (ship-based, AUV- or ROV-based), the beam angle of the system itself, the survey speed, and the distance to the seafloor. Significant advances in system accuracy, processing power and new software make multibeam mapping a powerful tool for studying sediment dynamics in 4D through repeated surveys that are ideally linked to additional studies on currents and sediment load in the water column. The Texelstroom channel, which is part of the Marsdiep between the city of Den Helder and the island of Texel (North Holland, the Netherlands), has been investigated in such a way for many years using water depth estimates from an ADCP installed on a ferry shuttling 24 times a day between the mainland and the island. Since 2009, repeated multibeam surveys have been undertaken up to three times per year as part of a student course, revealing sediment dynamics in much more detail than could be previously seen with the water depth estimates from the ferry-based ADCP. In the Texelstroom channel, the water depth ranges from a few meters to 45 meters. In the highly variable bathymetry, a series of large, bended sand waves exist mainly perpendicular to the direction of the main current. The shape of the sand waves changes from asymmetrical to symmetrical depending on the time of year, with more symmetrical shapes in spring and summer. Perpendicular to the large sand waves, smaller ripples develop during autumn. In addition to these changes in sand wave characteristics, sand wave crests sometimes migrate more than 30m in two months with an average movement of half a meter per day. The migration direction changes during the year resulting in a non-constant back-and-forth movement of the large sand waves. These intra-annual variations are characterized by changes in the slope of the sand waves, variations in the

  13. Analysis of Short Tandem Repeats by Parallel DNA Threading

    PubMed Central

    Zajac, Pawel; Öberg, Christine; Ahmadian, Afshin

    2009-01-01

    The majority of studies employing short tandem repeats (STRs) require investigation of several of these genetic markers. As such, we demonstrate the feasibility of the trinucleotide threading (TnT) approach for scalable analysis of STRs. The TnT method represents a parallel amplification alternative that addresses the obstacles associated with multiplex PCR. In this study, analysis of the STR fragments was performed with capillary gel electrophoresis; however, it should be possible to combine our approach with the massive 454 sequencing platform to considerably increase the number of targeted STRs. PMID:19915680

  14. Approaching infinite temperature upon repeated measurements of a quantum system

    SciTech Connect

    Yi, Juyeon; Talkner, Peter; Ingold, Gert-Ludwig

    2011-09-15

    The influence of repeated projective measurements on the dynamics of the state of a quantum system is studied as a function of the time lag {tau} between successive measurements. In the limit of infinitely many measurements of the occupancy of a single state the total system approaches a uniform state. The asymptotic approach to this state is exponential in the case of finite Hilbert space dimension. The rate characterizing this approach undergoes a sharp transition from a monotonically increasing to an erratically varying function of the time between subsequent measurements.

  15. UAVSAR: Airborne L-band Radar for Repeat Pass Interferometry

    NASA Technical Reports Server (NTRS)

    Moes, Timothy R.

    2009-01-01

    The primary objectives of the UAVSAR Project were to: a) develop a miniaturized polarimetric L-band synthetic aperture radar (SAR) for use on an unmanned aerial vehicle (UAV) or piloted vehicle. b) develop the associated processing algorithms for repeat-pass differential interferometric measurements using a single antenna. c) conduct measurements of geophysical interest, particularly changes of rapidly deforming surfaces such as volcanoes or earthquakes. Two complete systems were developed. Operational Science Missions began on February 18, 2009 ... concurrent development and testing of the radar system continues.

  16. [The repeated biopsy in patients with lupus nephritis].

    PubMed

    Subils, Gisella; Alba, Paula; Gobbi, Carla; Astesana, Pablo; Babini, Alejandra; Albiero, Eduardo

    2014-01-01

    We retrospectively studied patients with SLE according to ACR criteria, with NL who underwent a repeat renal biopsy from 2005 to 2012. We analyzed the main indications of renal biopsies, the histopathological Class and activity and chronicity changes. RESULTS The total number of patients with NL was 120, of which 18 (15%) patients underwent repeat renal biopsy, 18 had 2 renal biopsies and 6 had 3 biopsies. 3 (16.7%) patients were smokers; 1 (5.6%) had a history of previous DBT, 2 (11.1%) had a history of hypertension; and 3 (16.7%) patients had previous obesity. The duration of SLE was 15 ± 96 months; the time between the 1st and the 2nd biopsy was 45 ± 11 months and the time between the 2nd and 3rd biopsy was 56 ± 12 months. Indications for repeat biopsy were proteinuria in 10 biopsies (41.6%); proteinuria with impaired renal function in 2 biopsies (8.3%); proteinuria with pathological urine sediment in 8 (33.3%); . and pathological proteinuria with pathological urine sediment and impaired renal function in 4 biopsies (16.6%) The most frequent histological changes found between first and repeat biopsies were class IV to class III: 2 (8.2%) ; Class IV to Class IV: 8 (33.3%), class IV to class III + V: 2 (8.2%); class IV to class IV + V 3 (12.5%); class IV to class V: 2 (8.2%). Changes in NL biopsies with proliferative activity and chronicity indices (A / C) were: A to A / C: 7 (29.1%), A / C to A / C: 7 (29.1%). The immunosuppressive therapy was increased in 79.1% and 16.6% remained without changes. 20% patients received cyclophosphamide 1 g every 30 days, 26% Cyclophosphamide 500 mg every 15 days, 23% induction therapy with mycophenolate mofetil; 23% with Rituximab; 8% Cyclosporin A. Maintenance therapy with mycophenolate mofetil was performed in 87.5%; azathioprine in 1 case. Hydroxychloroquine was used in all cases.

  17. Semihierarchical quantum repeaters based on moderate lifetime quantum memories

    NASA Astrophysics Data System (ADS)

    Liu, Xiao; Zhou, Zong-Quan; Hua, Yi-Lin; Li, Chuan-Feng; Guo, Guang-Can

    2017-01-01

    The construction of large-scale quantum networks relies on the development of practical quantum repeaters. Many approaches have been proposed with the goal of outperforming the direct transmission of photons, but most of them are inefficient or difficult to implement with current technology. Here, we present a protocol that uses a semihierarchical structure to improve the entanglement distribution rate while reducing the requirement of memory time to a range of tens of milliseconds. This protocol can be implemented with a fixed distance of elementary links and fixed requirements on quantum memories, which are independent of the total distance. This configuration is especially suitable for scalable applications in large-scale quantum networks.

  18. Microdevice DNA forensics by the simple tandem repeat method.

    PubMed

    Goedecke, Nils; McKenna, Brian; El-Difrawy, Sameh; Gismondi, Elizabeth; Swenson, Abigail; Carey, Loucinda; Matsudaira, Paul; Ehrlich, Daniel J

    2006-04-14

    We review recent experiments on DNA forensics by the simple tandem repeat (STR) method using a 16-lane micromachined device as the active separation element. Separations by linear polyacrylamide matrices show very high data quality metrics when evaluated with statistically significant data sets. Full 16-locus multiplexes are verified on the multilane system. Multi-donor mixed samples are studied in the context of the limits of the laser-induced fluorescence detector and data-reduction software. The microdevice appears to be posed to outperform current capillary arrays in terms of stability and, through specialized sample loading, in the interpretation of complex mixtures.

  19. Repeat Descemetopexy after Descemet's Membrane Detachment following Phacoemulsification.

    PubMed

    Datar, Sameer; Kelkar, Aditya; Jain, Ashish K; Kelkar, Jai; Kelkar, Shreekant; Gandhi, Poonam; Shah, Rachna; Kedia, Ruchika

    2014-05-01

    Descemet's membrane detachment (DMD) is an uncommon condition with a wide range of possible etiologies. Probably the commonest cause is a localized detachment occurring after cataract extraction surgery. Descemetopexy gives good anatomic attachment rates and visual outcomes and has become the standard treatment for DMD. However, in cases with failed initial descemetopexy, the next step in the management of such cases remains unclear. Before initiating a complex surgical procedure like keratoplasty, which requires good postoperative care and regular follow-ups, repeat descemetopexy with a long-term tamponade using 14% C3F8 gas for recurrent DMD is definitely a worthwhile attempt.

  20. Serum cardiac troponin T after repeated endurance exercise events.

    PubMed

    Bonetti, A; Tirelli, F; Albertini, R; Monica, C; Monica, M; Tredici, G

    1996-05-01

    Recently Dr. Rowe made a hypothesis according to which small areas of myocardial necrosis can be caused by microvascular spasm, related to high catecholamine concentrations and other mechanisms, following extraordinary unremitting endurance exercises or due to the cumulative effect of several endurance events. It was this last suggestion which prompted us to investigate 25 top cyclists, taking part in the 77th Giro d'Italia. Blood samples were obtained the day before the start of the competition and once a week thereafter until the end. We measured myoglobin, lactic dehydrogenase, total creatine kinase, creatine kinase isoenzyme MB and serum cardiac troponin T (Tn-T), a highly sensitive and specific method for the detection of myocardial injury. While at measuring time points which followed we found a significant increase in the serum indicators of muscle damage, compared with their values at the beginning of the race, creatine kinase isoenzyme MB did not rise significantly and cardiac Tn-T was found in the serum of only 5 athletes, repeatedly in some cases, but always below the cut off values considered as indicating myocardial ischemia. On the basis of the behaviour of creatine kinase isoenzyme MB and, above all, of cardiac Tn-T, we can conclude that heavy endurance exercises, repeated daily for 22 days, as was the case in our study, do not seem able to produce, in top athletes, permanent heart damage by means of acute myocardial injury.

  1. Repeated Bout Effect in Muscle-Specific Exercise Variations.

    PubMed

    Zourdos, Michael C; Henning, Paul C; Jo, Edward; Khamoui, Andy V; Lee, Sang-Rok; Park, Young-Min; Naimo, Marshall; Panton, Lynn B; Nosaka, Kazunori; Kim, Jeong-Su

    2015-08-01

    A single bout of unaccustomed exercise confers protective effect against muscle damage from a subsequent bout of similar activity, that is, repeated bout effect (RBE). It remains unknown whether varying muscle-specific exercise between sessions alters the magnitude of the RBE. This study examined the effects of muscle-specific exercise variation between consecutive sessions on the RBE. Twenty untrained males (21 ± 2 years) were assigned to one of 2 groups (n = 10 per group): (a) 2 sessions of incline curls, Fixed Exercise or (b) 1 session of incline curls followed by 1 session of preacher curls, Varied Exercise, with 7 days between sessions. Subjects performed 5 sets of 6 repetitions at ∼50% of maximal isometric elbow flexor strength during each session. Changes in maximal voluntary isometric and isokinetic torque, range of motion, muscle soreness, and serum creatine kinase were measured before, immediately after, and 24, 48, 72, and 96 hours after each exercise session, and the changes were compared between bouts and between groups. There were significant time effects (p < 0.05) for isometric maximal voluntary contraction, concentric maximal voluntary contraction, range of motion, and muscle soreness during sessions 1 and 2 with no between-group differences. Both groups demonstrated a significantly faster recovery of range of motion and soreness to baseline levels after session 2 compared with session 1. Overall, our findings suggest that incline curls conferred a protective effect during subsequent preacher curls in a similar way to repeating incline curls; therefore, the RBE was not exercise specific.

  2. Large Torque Variations in Two Soft Gamma Repeaters

    NASA Technical Reports Server (NTRS)

    Woods, Peter M.; Kouveliotou, Chryssa; Gogus, Ersin; Finger, Mark H.; Swank, Jean; Markwardt, Craig B.; Hurley, Kevin; vanderKlis, Michiel

    2002-01-01

    We have monitored the pulse frequencies of the two soft gamma repeaters SGR 1806-20 and SGR 1900+14 through the beginning of year 2001 using primarily Rossi X-Ray Timing Explorer Proportional Counter Array observations. In both sources, we observe large changes in the spin-down torque up to a factor of approximately 4, which persist for several months. Using long-baseline phase-connected timing solutions as well as the overall frequency histories, we construct torque noise power spectra for each SGR (Soft Gamma Repeater). The power spectrum of each source is very red (power-law slope is approximately -3.5). The torque noise power levels are consistent with some accreting systems on timescales of approximately 1 yr, yet the full power spectrum is much steeper in frequency than any known accreting source. To the best of our knowledge, torque noise power spectra with a comparably steep frequency dependence have been seen only in young, glitching radio pulsars (e.g., Vela). The observed changes in spin-down rate do not correlate with burst activity; therefore, the physical mechanisms behind each phenomenon are also likely unrelated. Within the context of the magnetar model, seismic activity can not account for both the bursts and the long-term torque changes unless the seismically active regions are decoupled from one another.

  3. Labor union members play an OLG repeated game.

    PubMed

    Kandori, Michihiro; Obayashi, Shinya

    2014-07-22

    Humans are capable of cooperating with one another even when it is costly and a deviation provides an immediate gain. An important reason is that cooperation is reciprocated or rewarded and deviations are penalized in later stages. For cooperation to be sustainable, not only must rewards and penalties be strong enough but individuals should also have the right incentives to provide rewards and punishments. Codes of conduct with such properties have been studied extensively in game theory (as repeated game equilibria), and the literature on the evolution of cooperation shows how equilibrium behavior might emerge and proliferate in society. We found that community unions, a subclass of labor unions that admits individual affiliations, are ideal to corroborate these theories with reality, because (i) their activities are simple and (ii) they have a structure that closely resembles a theoretical model, the overlapping generations repeated game. A detailed case study of a community union revealed a possible equilibrium that can function under the very limited observability in the union. The equilibrium code of conduct appears to be a natural focal point based on simple heuristic reasoning. The union we studied was created out of necessity for cooperation, without knowing or anticipating how cooperation might be sustained. The union has successfully resolved about 3,000 labor disputes and created a number of offspring.

  4. Repeat aortocoronary bypass grafting. Early and late results.

    PubMed

    Kobayashi, T; Mendez, A M; Zubiate, P; Vanstrom, N R; Yokoyama, T; Kay, J H

    1978-04-01

    Seventy-nine patients underwent repeat myocardial revascularization between March 1971 and January 1977. The initial procedure was performed at the St. Vincent Medical Center, Los Angeles, in 70 (2.0 percent) of 3,526 patients undergoing surgery for coronary arterial disease and in nine more patients was performed at other hospitals; the second operation followed the first procedure at an interval of from three weeks to 78 months. Five deaths (6 percent) occurred while patients were hospitalized, and six deaths (8 percent) occurred later. Two of the six later deaths were from noncardiac causes. Complications were not different from those that occurred during primary procedures. Thirty-six (60 percent) of 60 patients undergoing repeat surgery since 1973 did not receive any transfusions of blood during or after surgery. Of 48 patients followed-up for periods ranging from 12 to 70 months after the second operation, angina was completely relieved in 18 patients (38 percent), improved in 16 patients (33 percent), unchanged in 11 patients (23 percent), and worse in three patients (6 percent).

  5. High teleportation rates using Rydberg-based quantum repeaters

    NASA Astrophysics Data System (ADS)

    Solmeyer, Neal; Quraishi, Qudsia

    2015-05-01

    Quantum networking over long distances may be achieved using repeater protocols to generate entanglement between memory nodes. Typically, long-lived memories have low entanglement generation rates. Neutral atom memories can be long-lived, emit at visible wavelengths and can be collectively excited leading to directionally emitted entangled photons. Here, we propose a simplified Rydberg-based quantum repeater based on recent work, where we reduce the number of ground states used for entanglement generation and use only one ensemble at each node, reducing the required resources. The collective excitation allows for deterministic memory generation that is mapped into a directionally emitted photonic qubit without the use of a high finesse optical cavity. We demonstrate a protocol between multiple memories stored within a single ensemble to implement a two-qubit gate. Additionally, we predict teleportation rates of 1 Hz without the use of a high finesse optical cavity, which could be increased to kHz if efficiencies are improved over the currently realized values. We plan to explore these protocols in ultra-cold ensemble of neutral 87Rb atoms and are currently building this setup.

  6. Precision orbit determination for the GEOSAT exact repeat mission

    NASA Astrophysics Data System (ADS)

    Smith, J. C.; Ries, J. C.; Shum, C. K.; Schutz, B. E.; Tapley, B. D.

    The Navy's Geodetic Satellite (GEOSAT) was launched on March 12, 1985, carrying a single-frequency microwave altimeter which measures the height of the satellite above the ocean surface to a precision of a few centimeters. The GEOSAT Exact Repeat Mission (ERM), which was initiated in November of 1986, placed the spacecraft in an exact 17 day repeat orbit. The Geophysical Data Records (GDR) for the ERM are available to the scientific community. GEOSAT is tracked by the Navy's OPNET and the Defense Mapping Agency's TRANET doppler tracking systems. The GDR orbits are computed using the OPNET tracking data and have an rms radial accuracy of one to two meters. The initial eighty days of the TRANET data during the ERM were made available for the assessment of the TRANET tracking system to perform precision orbit determination for the Topex/Poseidon Mission. This data was used to compute GEOSAT orbits using an improved gravity model which has been developed as part of the Topex gravity model improvement effort. Accuracy of the orbit was evaluated using altimeter crossover data. For a continuous 17 day GEOSAT orbit, the global crossover rms is at the 35 cm level, which suggests a radial orbit accuracy also on the order of 35 cm.

  7. Repeatability of surface EMG during gait in children

    PubMed Central

    Granata, Kevin P.; Padua, Darin A.; Abel, Mark F.

    2006-01-01

    Although mean amplitude and ON–OFF timing of muscle recruitment and electromyography (EMG) activation during gait is achieved by an age of six to eight years in normally developing children, recruitment dynamics illustrated by the shape of the EMG waveform may require continued developmental practice to achieve a stable pattern. Previous analyses have quantified the repeatability of the EMG waveform in adult subjects, but EMG variability for a pediatric population may be significantly different. The goal of this study was to quantify intra-session and inter-session variability in the phasic EMG waveform patterns from the lower limb muscles during self-selected speeds of walking in healthy-normal children for comparison with adult variability in gait EMG. The variance ratio quantifies the repeatability of the integrated EMG waveform shape in a group of normally-developing children. Results reveal that between-session EMG waveform variability were similar in adult and pediatric populations, but within-session variability for the children was approximately twice the published value for adults. Clinical implications of this pediatric EMG variability suggest cautious interpretation of data from limited trial samples or inter-session changes in performance of gait data. PMID:16274917

  8. The first crystal structure of an archaeal helical repeat protein

    SciTech Connect

    Yoneda, Kazunari; Sakuraba, Haruhiko; Tsuge, Hideaki; Katunuma, Nobuhiko; Kuramitsu, Seiki; Kawabata, Takeshi; Ohshima, Toshihisa

    2005-07-01

    The crystal structure of ST1625p, a protein encoded by a hypothetical open reading frame ST1625 in the genome of the hyperthermophilic archaeon Sulfolobus tokodaii, was determined at 2.2 Å resolution. The structure of ST1625p consists of a unique superhelix with a low-level structure resemblance to doamins from other proteins with known three-dimensional structures. The crystal structure of ST1625p, a protein encoded by a hypothetical open reading frame ST1625 in the genome of the hyperthermophilic archaeon Sulfolobus tokodaii, was determined at 2.2 Å resolution. The only sequence similarity exhibited by the amino-acid sequence of ST1625p was a 33% identity with the sequence of SSO0983p from S. solfataricus. The 19 kDa monomeric protein was observed to consist of a right-handed superhelix assembled from a tandem repeat of ten α-helices. A structural homology search using the DALI and MATRAS algorithms indicates that this protein can be classified as a helical repeat protein.

  9. Repeated tourniquet testing as a diagnostic tool in dengue infection.

    PubMed

    Norlijah, O; Khamisah, A Nor; Kamarul, A; Paeds, M; Mangalam, S

    2006-03-01

    Prospective evaluation of repeated standard tourniquet testing as a diagnostic indicator of dengue infection was done. Included were patients admitted to a children's hospital in Kuala Lumpur on a clinical suspicion of dengue infection based on the World Health Organization (WHO) criteria. A standard method of tourniquet was performed on 79 patients on a daily basis following admission. subjects and negative in the remaining 14 subjects. Fifty-eight subjects were serologically confirmed cases, 4 indeterminate and the remaining 17 subjects had negative serology. For diagnostic classification, 13 had dengue fever, 49 with dengue haemmorhagic fever (DHF) while 17 had non-dengue infection. The sensitivity and specificity of the tourniquet test was 82.8% and 23.5% respectively. The positive predictive value (PPV) was 78.7% while the negative predictive value (NPV) was 28.6%. In addition, the tourniquet test aided in the diagnosis of one-fifth of patients with DHF, who presented with a positive tourniquet test as the only bleeding manifestation. It seems that in a hospital setting, the tourniquet test adds little to the diagnosis of dengue infection/DHF. A positive tourniquet test, repeatedly performed, was found clinically useful as a preliminary screening test in dengue infection as recommended by WHO. However, it was not very specific and had a high false positive rate.

  10. A Case of Conjunctival Amyloidosis with Repeated Subconjunctival Hemorrhage

    PubMed Central

    Ando, Takaaki; Saito, Mamiko; Tawada, Ayako; Yotsukura, Jiro; Yamamoto, Shuichi

    2017-01-01

    Conjunctival amyloidosis is a very rare disease, and its presence may be a sign of systemic amyloidosis. We present our ocular and systemic findings in a patient with conjunctival amyloidosis. A 43-year-old man had repeated subconjunctival hemorrhages (SCHs) for two years and was referred to the Chiba University Hospital. He had comprehensive ophthalmological and systemic examinations to determine the cause of the SCHs. His visual acuities were 1.2 OU, and the intraocular pressures were 13-14 mmHg OU. Magnetic resonance imaging was normal. Initially, the SCH was the only abnormality. After 3 months, the SCH had partially cleared, and a pink mass was detected in the superior area of the subconjunctiva. Partial biopsy and histopathological examinations showed a greenish birefringence and dichroism under polarized light illumination. The birefringence was located in amyloid fibers. Immunofixation electrophoresis detected λ-light chain abnormality in the ocular biopsy specimen but systemic examinations did not find any lesions. Multiple myeloma was ruled out, and the patient is being followed closely to detect any early signs of systemic amyloidosis. Because repeated SCHs might be initial signs of systemic amyloidosis, patients with conjunctival amyloidosis should be comprehensively examined for systemic amyloidosis because of its poor life prognosis. PMID:28326212

  11. Evidence for a Creative Dilemma Posed by Repeated Collaborations

    PubMed Central

    Inoue, Hiroyasu

    2015-01-01

    We focused on how repeat collaborations in projects for inventions affect performance. Repeat collaborations have two contradictory aspects. A positive aspect is team development or experience, and a negative aspect is team degeneration or decline. Since both contradicting phenomena are observed, inventors have a dilemma as to whether they should keep collaborating in a team or not. The dilemma has not previously been quantitatively analyzed. We provide quantitative and extensive analyses of the dilemma in creative projects by using patent data from Japan and the United States. We confirm three predictions to quantitatively validate the existence of the dilemma. The first prediction is that the greater the patent a team achieves, the longer the team will work together. The second prediction is that the impact of consecutive patents decreases after a team makes a remarkable invention, which is measured by the impact of patents. The third prediction is that the expectation of impact with new teams is greater than that with the same teams successful in the past. We find these predictions are validated in patents published in Japan and the United States. On the basis of these three predictions, we can quantitatively validate the dilemma in creative projects. We also propose preventive strategies for degeneration. One is developing technological diversity, and another is developing inventor diversity in teams. We find the two strategies are both effective by validating with the data. PMID:26340441

  12. Labor union members play an OLG repeated game

    PubMed Central

    Kandori, Michihiro; Obayashi, Shinya

    2014-01-01

    Humans are capable of cooperating with one another even when it is costly and a deviation provides an immediate gain. An important reason is that cooperation is reciprocated or rewarded and deviations are penalized in later stages. For cooperation to be sustainable, not only must rewards and penalties be strong enough but individuals should also have the right incentives to provide rewards and punishments. Codes of conduct with such properties have been studied extensively in game theory (as repeated game equilibria), and the literature on the evolution of cooperation shows how equilibrium behavior might emerge and proliferate in society. We found that community unions, a subclass of labor unions that admits individual affiliations, are ideal to corroborate these theories with reality, because (i) their activities are simple and (ii) they have a structure that closely resembles a theoretical model, the overlapping generations repeated game. A detailed case study of a community union revealed a possible equilibrium that can function under the very limited observability in the union. The equilibrium code of conduct appears to be a natural focal point based on simple heuristic reasoning. The union we studied was created out of necessity for cooperation, without knowing or anticipating how cooperation might be sustained. The union has successfully resolved about 3,000 labor disputes and created a number of offspring. PMID:25024211

  13. Extensive telomere repeat arrays in mouse are hypervariable.

    PubMed Central

    Starling, J A; Maule, J; Hastie, N D; Allshire, R C

    1990-01-01

    In this study we have analysed mouse telomeres by Pulsed Field Gel Electrophoresis (PFGE). A number of specific restriction fragments hybridising to a (TTA-GGG)4 probe in the size range 50-150kb can be detected. These fragments are devoid of sites for most restriction enzymes suggesting that they comprise simple repeats; we argue that most of these are likely to be (TTAGGG)n. Each discrete fragment corresponds to the telomere of an individual chromosome and segregates as a Mendelian character. However, new size variants are being generated in the germ line at very high rates such that inbred mice are heterozygous at all telomeres analysable. In addition we show that specific small (approximately 4-12kb) fragments can be cleaved within some terminal arrays by the restriction enzyme MnII which recognises 5'(N7)GAGG3'. Like the complete telomere-repeat arrays (TRA's) these fragments form new variants at high rates and possibly by the same process. We speculate on the mechanisms that may be involved. Images PMID:2175882

  14. Reactor pulse repeatability studies at the annular core research reactor

    SciTech Connect

    DePriest, K.R.; Trinh, T.Q.; Luker, S. M.

    2011-07-01

    The Annular Core Research Reactor (ACRR) at Sandia National Laboratories is a water-moderated pool-type reactor designed for testing many types of objects in the pulse and steady-state mode of operations. Personnel at Sandia began working to improve the repeatability of pulse operations for experimenters in the facility. The ACRR has a unique UO{sub 2}-BeO fuel that makes the task of producing repeatable pulses difficult with the current operating procedure. The ACRR produces a significant quantity of photoneutrons through the {sup 9}Be({gamma}, n){sup 8}Be reaction in the fuel elements. The photoneutrons are the result of the gammas produced during fission and in fission product decay, so their production is very much dependent on the reactor power history and changes throughout the day/week of experiments in the facility. Because the photoneutrons interfere with the delayed-critical measurements required for accurate pulse reactivity prediction, a new operating procedure was created. The photoneutron effects at delayed critical are minimized when using the modified procedure. In addition, the pulse element removal time is standardized for all pulse operations with the modified procedure, and this produces less variation in reactivity removal times. (authors)

  15. Recency, repeatability, and reinforcer retrenchment: an experimental analysis of resurgence.

    PubMed

    Lieving, Gregory A; Lattal, Kennon A

    2003-09-01

    Four experiments were conducted with pigeons to assess the experimental conditions necessary for the occurrence of resurgence. The general procedure consisted of the following conditions: Condition 1--reinforcement of key pecking; Condition 2--reinforcement of treadle pressing and concurrent extinction of key pecking; and Condition 3--the resurgence condition wherein resurgence was defined as the recovery of key pecking. In Experiments 1 and 2, the resurgence condition was conventional extinction. The effect of recency on resurgence magnitude was examined in Experiment 1 by manipulating the number of sessions of Condition 2, above. Resurgence was not a function of recency with the parameters used. Repeating the three conditions revealed resurgence to be a repeatable effect in Experiment 2. In Experiment 3, a variable-time schedule was in effect for the resurgence condition. Resurgence was not produced by response-independent food delivery. In Experiment 4, the resurgence condition was a variable-interval schedule for treadle pressing that arranged a lower reinforcement rate than in Condition 2 (92% reduction in reinforcers per minute). Resurgence was lower in magnitude relative to conventional extinction, although resurgence was obtained with 2 out of 3 pigeons. The results are discussed in terms of the variables controlling resurgence and the relations between behavioral history, resurgence, and other forms of response recovery.

  16. Evidence for a Creative Dilemma Posed by Repeated Collaborations.

    PubMed

    Inoue, Hiroyasu

    2015-01-01

    We focused on how repeat collaborations in projects for inventions affect performance. Repeat collaborations have two contradictory aspects. A positive aspect is team development or experience, and a negative aspect is team degeneration or decline. Since both contradicting phenomena are observed, inventors have a dilemma as to whether they should keep collaborating in a team or not. The dilemma has not previously been quantitatively analyzed. We provide quantitative and extensive analyses of the dilemma in creative projects by using patent data from Japan and the United States. We confirm three predictions to quantitatively validate the existence of the dilemma. The first prediction is that the greater the patent a team achieves, the longer the team will work together. The second prediction is that the impact of consecutive patents decreases after a team makes a remarkable invention, which is measured by the impact of patents. The third prediction is that the expectation of impact with new teams is greater than that with the same teams successful in the past. We find these predictions are validated in patents published in Japan and the United States. On the basis of these three predictions, we can quantitatively validate the dilemma in creative projects. We also propose preventive strategies for degeneration. One is developing technological diversity, and another is developing inventor diversity in teams. We find the two strategies are both effective by validating with the data.

  17. Brokering as a framework for hydrological model repeatability

    NASA Astrophysics Data System (ADS)

    Fuka, Daniel; Collick, Amy; MacAlister, Charlotte; Braeckel, Aaron; Wright, Dawn; Jodha Khalsa, Siri; Boldrini, Enrico; Easton, Zachary

    2015-04-01

    Data brokering aims to provide those in the the sciences with quick and repeatable access to data that represents physical, biological, and chemical characteristics; specifically to accelerate scientific discovery. Environmental models are useful tools to understand the behavior of hydrological systems. Unfortunately, parameterization of these hydrological models requires many different data, from different sources, and from different disciplines (e.g., atmospheric, geoscience, ecology). In basin scale hydrological modeling, the traditional procedure for model initialization starts with obtaining elevation models, land-use characterizations, soils maps, and weather data. It is often the researcher's past experience with these datasets that determines which datasets will be used in a study, and often newer, or more suitable data products will exist. An added complexity is that various science communities have differing data formats, storage protocols, and manipulation methods, which makes use by a non native user exceedingly difficult and time consuming. We demonstrate data brokering as a means to address several of these challenges. We present two test case scenarios in which researchers attempt to reproduce hydrological model results using 1) general internet based data gathering techniques, and 2) a scientific data brokering interface. We show that data brokering can increase the efficiency with which data are obtained, models are initialized, and results are analyzed. As an added benefit, it appears brokering can significantly increase the repeatability of a given study.

  18. Molecular identity of ramie germplasms using simple sequence repeat markers.

    PubMed

    Luan, M B; Chen, B F; Zou, Z Z; Zhu, J J; Wang, X F; Xu, Y; Sun, Z M; Chen, J H

    2015-03-27

    DNA identity is highly effective and efficient for distinguishing crop varieties regardless of their phenotypic similarities. To establish DNA identity in ramie, 21 simple sequence repeat primers were amplified in 108 accessions of domestic and exotic ramie germplasms. Sixty polymorphic bands were obtained, with an average of 2.9 bands per locus and 2-8 band types per primer locus (average of 5.19 band types). The Simpson's diversity index of the 21 simple sequence repeat loci ranged from 0.158 to 0.808 with an average of 0.612. There was large difference in the specific index in the germplasm tested, from 44.082 to 218.163, with an average of 83.620. Based on allele band type, 8 primer pairs were selected for DNA fingerprinting of the 108 genotypes. The combination of the 8 primer pairs were found to be very effective for distinguishing these genotypes, indicating that they can be used in the molecular DNA identity of ramie.

  19. A WD-Repeat Protein Stabilizes ORC Binding to Chromatin

    PubMed Central

    Shen, Zhen; Sathyan, Kizhakke M.; Geng, Yijie; Zheng, Ruiping; Chakraborty, Arindam; Freeman, Brian; Wang, Fei; Prasanth, Kannanganattu V.; Prasanth, Supriya G.

    2015-01-01

    SUMMARY Origin recognition complex (ORC) plays critical roles in the initiation of DNA replication and cell-cycle progression. In metazoans, ORC associates with origin DNA during G1 and with heterochromatin in postreplicated cells. However, what regulates the binding of ORC to chromatin is not understood. We have identified a highly conserved, leucine-rich repeats and WD40 repeat domain-containing protein 1 (LRWD1) or ORC-associated (ORCA) in human cells that interacts with ORC and modulates chromatin association of ORC. ORCA colocalizes with ORC and shows similar cell-cycle dynamics. We demonstrate that ORCA efficiently recruits ORC to chromatin. Depletion of ORCA in human primary cells and embryonic stem cells results in loss of ORC association to chromatin, concomitant reduction of MCM binding, and a subsequent accumulation in G1 phase. Our results suggest ORCA-mediated association of ORC to chromatin is critical to initiate preRC assembly in G1 and chromatin organization in post-G1 cells. PMID:20932478

  20. Triplet repeat primed PCR simplifies testing for Huntington disease.

    PubMed

    Jama, Mohamed; Millson, Alison; Miller, Christine E; Lyon, Elaine

    2013-03-01

    Diagnostic and predictive testing for Huntington disease (HD) requires an accurate determination of the number of CAG repeats in the Huntingtin (HHT) gene. Currently, when a sample appears to be homozygous for a normal allele, additional testing is required to confirm amplification from both alleles. If the sample still appears homozygous, Southern blot analysis is performed to rule out an undetected expanded HTT allele. Southern blot analysis is expensive, time-consuming, and labor intensive and requires high concentrations of DNA. We have developed a chimeric PCR process to help streamline workflow; true homozygous alleles are easily distinguished by this simplified method, and only very large expanded alleles still require Southern blot analysis. Two hundred forty-six HD samples, previously run with a different fragment analysis method, were analyzed with our new method. All samples were correctly genotyped, resulting in 100% concordance between the methods. The chimeric PCR assay was able to identify expanded alleles up to >150 CAG repeats. This method offers a simple strategy to differentiate normal from expanded CAG alleles, thereby reducing the number of samples reflexed to Southern blot analysis. It also provides assurance that expanded alleles are not routinely missed because of allele dropout.

  1. Gibbs motif sampling: detection of bacterial outer membrane protein repeats.

    PubMed Central

    Neuwald, A. F.; Liu, J. S.; Lawrence, C. E.

    1995-01-01

    The detection and alignment of locally conserved regions (motifs) in multiple sequences can provide insight into protein structure, function, and evolution. A new Gibbs sampling algorithm is described that detects motif-encoding regions in sequences and optimally partitions them into distinct motif models; this is illustrated using a set of immunoglobulin fold proteins. When applied to sequences sharing a single motif, the sampler can be used to classify motif regions into related submodels, as is illustrated using helix-turn-helix DNA-binding proteins. Other statistically based procedures are described for searching a database for sequences matching motifs found by the sampler. When applied to a set of 32 very distantly related bacterial integral outer membrane proteins, the sampler revealed that they share a subtle, repetitive motif. Although BLAST (Altschul SF et al., 1990, J Mol Biol 215:403-410) fails to detect significant pairwise similarity between any of the sequences, the repeats present in these outer membrane proteins, taken as a whole, are highly significant (based on a generally applicable statistical test for motifs described here). Analysis of bacterial porins with known trimeric beta-barrel structure and related proteins reveals a similar repetitive motif corresponding to alternating membrane-spanning beta-strands. These beta-strands occur on the membrane interface (as opposed to the trimeric interface) of the beta-barrel. The broad conservation and structural location of these repeats suggests that they play important functional roles. PMID:8520488

  2. Sensitization of locomotion following repeated ventral tegmental injections of cytisine.

    PubMed

    Museo, E; Wise, R A

    1994-06-01

    Systemic injections of nicotine increase locomotion, and repeating these injections brings about a sensitization of the locomotor response. Ventral tegmental injections of the nicotinic agonist cytisine also increase locomotion. In the present study cytisine was administered repeatedly into the ventral tegmentum to determine whether sensitization of its locomotor-activating effects would develop. Four groups of animals were tested; each group received a total of six injections at a rate of one injection every 48 h. Two of these groups received injections of cytisine (10 nmol/side): one group received injections into the ventral tegmentum, and, to insure the anatomical specificity of the locomotor effect, a second group received injections dorsal to the ventral tegmentum. The remaining two groups received vehicle injections: one group received injections into the ventral tegmentum, and the other received injections into more dorsal sites. The group of animals that received injections of cytisine into the ventral tegmentum locomoted more than any other group. In addition, only with this group was a progressive increase in the locomotor response evident across test days. These findings raise the possibility that a neural substrate in the ventral tegmentum mediates the locomotor-activating and sensitizing effects associated with the systemic administration of nicotine.

  3. Novel mutational mechanism in man: Expansion of trinucleotide repeats

    SciTech Connect

    Ilarioshkin, S.N.; Ivanova-Smolenskaya, I.A.; Markova, E.D.

    1995-11-01

    An analysis of a novel, recently discovered class of mutations in man - an expansion, i.e., an increase of the copy number of intragenic unstable trinucleotide repeats - is presented. The expansion of trinucleotide X chromosome syndrome (two separate variants of the disease - FRAXA and FRAXE), myotonic dystrophy, spinal and bulbar Kennedy`s amyotrophy, Huntington`s chorea, type 1 spinocerebellar ataxia, and dentatorubral-pallidolyusian atrophy. The discovery of triplet expansion allows a satisfactory explanation on the molecular level of a series of unusual clinical genetic phenomena, such as anticipation, the {open_quotes}paternal transmission{close_quotes} effect, the {open_quotes}Sherman paradox,{close_quotes} and others. The common properties and the distinctions of unstable trinucleotide mutations in the nosologic forms mentioned above are analyzed comprehensively. These features include the mechanism by which these mutations cause disease, the time of their appearance in ontogenesis, and various clinical genetic correlations. The evolutionary origin of this class of mutations and, in particular, the role of alleles with an {open_quotes}intermediate{close_quotes} triplet number, which are the persistent reservoir of mutations arising de novo in a population, are also discussed. The possible implication of unstable trinucleotide repeats for a series of other hereditary diseases, such as type 2, spinocerebellar ataxia, Machado-Joseph disease, hereditary spastic paraplegia, essential tremor, schizophrenia, and others, is also suggested. 108 refs., 1 tab.

  4. Repeatability and reproducibility of aquatic testing with zinc dithiophosphate

    SciTech Connect

    Hooter, D.L.; Hoke, D.I.; Kraska, R.C.; Wojewodka, R.A.

    1994-12-31

    This testing program was designed to characterize the repeatability and reproducibility of aquatic screening studies with a water insoluble chemical substance. Zinc dithiophosphate was selected for its limited water solubility and moderate aquatic toxicity. Acute tests were conducted using fathead minnows and Daphnia magna, according to guidelines developed to minimize random sources of non-repeatability. Zinc dithiosphosphate was exposed to the organisms in static tests using an oil-water dispersion method for the fathead minnows, and a water-accommodated-fraction method for the Daphnia magna. Testing was conducted in moderately hard water with pre-determined nominal concentrations of 0. 1, 1.0, 10.0, 100.00, and 1000.0 ppm or ppm WAF. 24 studies were contracted among 3 separate commercial contract laboratories. The program results demonstrate the diverse range of intralaboratory and interlaboratory variability based on the organism type, and emphasize the need for further study and caution in the design, and implementation of aquatic testing for insoluble materials.

  5. Repeatability and heritability of response to superovulation in Holstein cows.

    PubMed

    Tonhati, H; Lôbo, R B; Oliveira, H N

    1999-04-15

    The objective of this study was to estimate the relative effects of genetic and phenotypic factors on the efficacy and efficiency of superovulation for Holstein-Friesian cows reared in Brazil. A database, established by the Associacao Brasileira de Criadores de Bovinos da Raca Holandesa, consisting of a total of 5387 superovulations of 2941 cows distributed over 473 herds and sired by 690 bulls was used for the analysis. The records were analyzed by MTDFREML (Multiple Trait Derivative-Free Restricted Maximum Likelihood), using a repeatability animal model. The fixed effects included in the model were contemporaneous group (veterinarian, herd, year and season of the superovulation); number of semen doses; cow age; and superovulation order. The estimated repeatability of the number of the transferable embryos was low (0.13), and the estimated heritability was 0.03. These results indicate that environmental factors play a critical role in the response of a cow to a superovulation treatment. There is little evidence that future responses to superovulation by individual females can be predicted by previous treatment(s) or that superovulation response is an heritable trait.

  6. Maximum likelihood decoding analysis of Accumulate-Repeat-Accumulate Codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    Repeat-Accumulate (RA) codes are the simplest turbo-like codes that achieve good performance. However, they cannot compete with Turbo codes or low-density parity check codes (LDPC) as far as performance is concerned. The Accumulate Repeat Accumulate (ARA) codes, as a subclass of LDPC codes, are obtained by adding a pre-coder in front of RA codes with puncturing where an accumulator is chosen as a precoder. These codes not only are very simple, but also achieve excellent performance with iterative decoding. In this paper, the performance of these codes with (ML) decoding are analyzed and compared to random codes by very tight bounds. The weight distribution of some simple ARA codes is obtained, and through existing tightest bounds we have shown the ML SNR threshold of ARA codes approaches very closely to the performance of random codes. We have shown that the use of precoder improves the SNR threshold but interleaving gain remains unchanged with respect to RA code with puncturing.

  7. Gaussian-only regenerative stations cannot act as quantum repeaters

    NASA Astrophysics Data System (ADS)

    Namiki, Ryo; Gittsovich, Oleg; Guha, Saikat; Lütkenhaus, Norbert

    2014-12-01

    Higher transmission loss diminishes the performance of optical communication—be it the rate at which classical or quantum data can be sent reliably, or the secure key generation rate of quantum key distribution (QKD). Loss compounds with distance—exponentially in an optical fiber, and inverse square with distance for a free-space channel. In order to boost classical communication rates over long distances, it is customary to introduce regenerative relays at intermediate points along the channel. It is therefore natural to speculate whether untended regenerative stations, such as phase-insensitive or phase-sensitive optical amplifiers, could serve as repeaters for long-distance QKD. The primary result of this paper rules out all bosonic Gaussian channels to be useful as QKD repeaters, which include phase-insensitive and phase-sensitive amplifiers as special cases, for any QKD protocol. We also delineate the conditions under which a Gaussian relay renders a lossy channel entanglement breaking, which in turn makes the channel useless for QKD.

  8. Repeat-based Sequence Typing of Carnobacterium maltaromaticum.

    PubMed

    Rahman, Abdur; El Kheir, Sara M; Back, Alexandre; Mangavel, Cécile; Revol-Junelles, Anne-Marie; Borges, Frédéric

    2016-06-02

    Carnobacterium maltaromaticum is a Lactic Acid Bacterium (LAB) of technological interest for the food industry, especially the dairy as bioprotection and ripening flora. The industrial use of this LAB requires accurate and resolutive typing tools. A new typing method for C. maltaromaticum inspired from MLVA analysis and called Repeat-based Sequence Typing (RST) is described. Rather than electrophoresis analysis, our RST method is based on sequence analysis of multiple loci containing Variable-Number Tandem-Repeats (VNTRs). The method described here for C. maltaromaticum relies on the analysis of three VNTR loci, and was applied to a collection of 24 strains. For each strain, a PCR product corresponding to the amplification of each VNTR loci was sequenced. Sequence analysis allowed delineating 11, 11, and 12 alleles for loci VNTR-A, VNTR-B, and VNTR-C, respectively. Considering the allele combination exhibited by each strain allowed defining 15 genotypes, ending in a discriminatory index of 0.94. Comparison with MLST revealed that both methods were complementary for strain typing in C. maltaromaticum.

  9. A designed repeat protein as an affinity capture reagent.

    PubMed

    Speltz, Elizabeth B; Brown, Rebecca S H; Hajare, Holly S; Schlieker, Christian; Regan, Lynne

    2015-10-01

    Repeat proteins are an attractive target for protein engineering and design. We have focused our attention on the design and engineering of one particular class: tetratricopeptide repeat (TPR) proteins. In previous work, we have shown that the structure and stability of TPR proteins can be manipulated in a rational fashion [Cortajarena (2011) Prot. Sci. 20: , 1042-1047; Main (2003) Structure 11: , 497-508]. Building on those studies, we have designed and characterized a number of different peptide-binding TPR modules and we have also assembled these modules into supramolecular arrays [Cortajarena (2009) ACS Chem. Biol. 5: , 545-552; Cortajarena (2008) ACS Chem. Biol. 3: , 161-166; Jackrel (2009) Prot. Sci. 18: , 762-774; Kajander (2007) Acta Crystallogr. D Biol. Crystallogr. 63: , 800-811]. Here we focus on the development of one such TPR-peptide interaction for a practical application, affinity purification. We illustrate the general utility of our designed protein interaction. Furthermore, this example highlights how basic research on protein-peptide interactions can lead to the development of novel reagents with important practical applications.

  10. Repeated Pesticide Exposure among North Carolina Migrant and Seasonal Farmworkers

    PubMed Central

    Arcury, Thomas A.; Grzywacz, Joseph G.; Talton, Jennifer W.; Chen, Haiying; Vallejos, Quirina M.; Galvan, Leonardo; Barr, Dana B.; Quandt, Sara A.

    2010-01-01

    Background Limited data document the multiple and repeated pesticide absorption experienced by farmworkers in an agricultural season or their risk factors. Methods Data were collected from 196 farmworkers 4 times at monthly intervals in 2007. Urine samples were tested for 12 pesticide urinary metabolites. Questionnaire data provided measures of exposure risks. Results Farmworkers had at least one detection for many pesticide urinary metabolites; e.g. 84.2% had at least one detection for acephate, 88.8% for 3,5,6-trichloro-2-pyridinol. Most farmworkers had multiple detections for specific metabolites; e.g., 64.8% had 2 or more detections for acephate, 64.8% for 3,5,6-trichloro-2-pyridinol, 79.1% for 3-phenoxybenzoic acid, and 86.7% for 2,4-dichlorophenoxyacetic acid. Housing type had a consistent significant association with metabolite detections. Conclusions Farmworkers are exposed to multiple pesticides across an agricultural season, and they experience repeated exposures to the same pesticides. Reducing farmworker pesticide exposure and delineating the health outcomes of this exposure require more detailed data. PMID:20623661

  11. Cybersickness Following Repeated Exposure to DOME and HMD Virtual Environments

    NASA Technical Reports Server (NTRS)

    Taylor, Laura C.; Harm, Deborah L.; Kennedy, Robert S.; Reschke, Millard F.; Loftin, R. Bowen

    2011-01-01

    Virtual environments (VE) offer unique training opportunities, including training astronauts to preadapt them to the novel sensory conditions of microgravity. However, one unresolved issue with VE use is the occurrence of cybersickness during and following exposure to VE systems. Most individuals adapt and become less ill with repeated interaction with VEs. The goal of this investigation was to compare motion sickness symptoms (MSS) produced by dome and head-mounted (HMD) displays and to examine the effects of repeated exposures on MSS. Sixty-one subjects participated in the study. Three experimental sessions were performed each separated by one day. The subjects performed a navigation and pick and place task in either a dome or HMD VE. MSS were measured using a Simulator Sickness Questionnaire before, immediately after, and at 1, 2, 4 and 6 hours following exposure to the VEs. MSS data were normalized by calculating the natural log of each score and an analysis of variance was performed. We observed significant main effects for day and time and a significant day by time interaction for total sickness and for each of the subscales, nausea, oculomotor and disorientation. However, there was no significant main effect for device. In conclusion, subjects reported a large increase in MSS immediately following exposure to both the HMD and dome, followed by a rapid recovery across time. Sickness severity also decreased over days, which suggests that subjects become dual-adapted over time making VE training a viable pre-flight countermeasure for space motion sickness.

  12. Motion of an Antarctic glacier by repeated tidally modulated earthquakes

    NASA Astrophysics Data System (ADS)

    Zoet, Lucas K.; Anandakrishnan, Sridhar; Alley, Richard B.; Nyblade, Andrew A.; Wiens, Douglas A.

    2012-09-01

    Between debris-laden glacial ice and bedrock, basal seismicity can develop that yields information about bed properties, stress distribution, outburst flooding, and crevassing and calving. Basal seismicity in response to glacial motion is linked to variations in both stress and lubrication of bedrock by water and till. Here we analyse data from the Transantarctic Mountains Seismic Experiment array in 2002-2003 to investigate seismic behaviour at David Glacier, a large outlet glacier that drains 4% of East Antarctica's ice sheet into the Ross Sea. We identify about 20,000 seismic events that are larger in magnitude and duration than typical for glacial sources and repeat at regular intervals of about 25min. These events are consistent with stick-slip behaviour of debris-laden ice moving over a single obstacle of rough bedrock, modulated by relatively small stress changes from the ocean tides. In the years before and after the interval of repeating events, seismic events with irregular and generally longer intervals were detected at the same location, and are consistent with combined stick-slip and continuous sliding of the subglacial interface. We suggest that the observed transitions in seismicity patterns capture the dynamic behaviour of the ice stream, and that--despite lower ice-flow velocities--sliding in the stick-slip regime enhances subglacial erosion.

  13. Repeated-drive adaptive feedback identification of network topologies.

    PubMed

    Yang, Pu; Zheng, Zhigang

    2014-11-01

    The identification of the topological structures of complex networks from dynamical information is a significant inverse problem. How to infer the information of network topology from short-time dynamical data is a challenging topic. The presence of synchronization among nodes makes the identification of network topology difficult. In this paper we present an efficient method called the repeated-drive adaptive feedback scheme to reveal the network connectivity from short-time dynamics. By applying the short asynchronous transient data as a repeated drive, the adjacency matrix can be successfully determined in terms of the modified adaptive feedback scheme. This improved scheme is valid for both synchronous and asynchronous cases of the network and is especially efficient in the presence of global or local synchronization, where the transient drive can be obtained by perturbing the system to get a very short asynchronous transient. The detection speed of our scheme exhibits the optimized effect by adjusting the time-series segment length and the coupling strength among nodes in the network.

  14. The C9ORF72 repeat expansion disrupts nucleocytoplasmic transport

    PubMed Central

    Haeusler, Aaron R.; Grima, Jonathan C.; Machamer, James B.; Steinwald, Peter; Daley, Elizabeth L.; Miller, Sean J.; Cunningham, Kathleen M.; Vidensky, Svetlana; Gupta, Saksham; Thomas, Michael A.; Hong, Ingie; Chiu, Shu-Ling; Huganir, Richard L.; Ostrow, Lyle W.; Matunis, Michael J.; Wang, Jiou; Sattler, Rita

    2016-01-01

    A GGGGCC (G4C2) hexanucleotide repeat expansion (HRE) in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies support an HRE RNA gain-of-function mechanism of neurotoxicity, and we previously identified protein interactors for the G4C2 RNA including RanGAP1. A candidate-based genetic screen in Drosophila expressing 30 G4C2 repeats identified RanGAP (Drosophila ortholog of human RanGAP1), a key regulator of nucleocytoplasmic transport, as a potent suppressor of neurodegeneration. Enhancing nuclear import or suppressing nuclear export of proteins also suppresses neurodegeneration. RanGAP physically interacts with HRE RNA and is mislocalized in HRE-expressing flies, neurons from C9ORF72 ALS patient-derived induced pluripotent stem cells (iPSNs), and in C9ORF72 patient brain tissue. Nuclear import is impaired as a result of HRE expression in the fly model and in C9ORF72 iPSNs, and these deficits are rescued by small molecules and antisense oligonucleotides targeting the HRE G-quadruplexes. Nucleocytoplasmic transport defects may be a fundamental pathway for ALS and FTD amenable to pharmacotherapeutic intervention. PMID:26308891

  15. Deletion in the FMR1 gene in a fragile-X male

    SciTech Connect

    Mannermaa, A.; Pulkkinen, L.; Kajanoja, E.

    1996-08-09

    The pathogenesis of fragile-X syndrome is a consequence of absence of the FMR1 gene product associated with expansion of the CGG repeat and abnormal methylation of this and a CpG island 250 hp proximal to the CGG repeat located at exon 1 in the FMR1 gene. While this is usually the case, some suspected fragile-X syndrome patients have been described with a mutation other than CGG expansion. We describe here an affected fragile-X male, who was found to be mosaic of a full mutation of the CGG expansion and a deletion in the FMR1 gene. The patient`s phenotype is probably mainly due to the effect of the full mutation of the repeat sequence. Thus, the influence of the deletion is difficult to evaluate. 20 refs., 2 figs.

  16. Repeat Head Hits May Not Put NFL Players at Risk of Motor Problems

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_163670.html Repeat Head Hits May Not Put NFL Players at Risk ... 19, 2017 (HealthDay News) -- Repeated hits to the head may not doom NFL players to suffer movement ...

  17. Screening for the presence of FMR1 premutation alleles in a Spanish population with fibromyalgia.

    PubMed

    Martorell, Loreto; Tondo, Mireia; Garcia-Fructuoso, Ferrán; Naudo, Montserrat; Alegre, Cayetano; Gamez, Josep; Genovés, Jordi; Poo, Pilar

    2012-11-01

    Fragile X mental retardation 1 (FMR1) premutation carriers, who are at risk of having children with fragile X Syndrome, were initially considered as clinically unaffected. However, recent clinical and molecular studies have shifted this point of view. The incidence of premutation in the general population is substantial. Apart from the well-documented fragile X-associated tremor-ataxia and fragile X premature ovarian insufficiency, there is a broad constellation of symptoms including depression, anxiety, muscle pain, autoimmune and thyroid disease, chronic fatigue, and fibromyalgia that has been described, particularly in females with the premutation (55-200 repeats). Fibromyalgia (FM) is the most common cause of widespread pain and comprises a heterogeneous group of patients, affecting 2-3 % of the general population. We analyzed the FMR1 gene in a cohort of females diagnosed with fibromyalgia in order to assess the incidence of premutated alleles. CGG repeat size was determined in 353 females suffering from FM and results were compared with a control group. Four premutated carriers in the FM group were detected. The observed incidence is higher than that described for a normal female population (1/88 vs 1/250). The early detection of premutation carriers for the FMR1 gene among individuals diagnosed with fibromyalgia is important and would be helpful in correct genetic counseling of patients and their families, who may be at risk of having children with fragile X syndrome, the most common known cause of inherited intellectual disability and autism. Our data should be cautiously interpreted based on just this study; nevertheless, screening for the FMR1 gene in FM patients at least with presentations suggestive of FMR1 gene-related disease seems recommendable.

  18. Exposing Students to Repeat Photography: Increasing Cultural Understanding on a Short-Term Study Abroad

    ERIC Educational Resources Information Center

    Lemmons, Kelly K.; Brannstrom, Christian; Hurd, Danielle

    2014-01-01

    Traditionally, repeat photography has been used to analyze land cover change. This paper describes how repeat photography may be used as a tool to enhance the short-term study abroad experience by facilitating cultural interaction and understanding. We present evidence from two cases and suggest a five-step repeat photography method for educators…

  19. 47 CFR 22.573 - Use of base transmitters as repeaters.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Use of base transmitters as repeaters. 22.573... of base transmitters as repeaters. As an additional function, base transmitters may be used as repeaters. Licensees must be able to turn the base transmitter on or off from the control point...

  20. 47 CFR 22.573 - Use of base transmitters as repeaters.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Use of base transmitters as repeaters. 22.573... of base transmitters as repeaters. As an additional function, base transmitters may be used as repeaters. Licensees must be able to turn the base transmitter on or off from the control point...